Bacteriology exam prep topics 10-12
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Questions and Answers

When was the term 'antibiotic' first used and by whom?

  • 1893 by Bartolomeo Gosio
  • 1890 by Paul Vuillemin (correct)
  • 1913 in the USA
  • 1995 by the US FDA

    • What was the first antibiotic to be discovered from nature?

  • Tetracycline
  • Streptomycin
  • Penicillin
  • Mycophenolic acid (correct)

    • What properties does mycophenolic acid possess?

  • Antiviral, antitumor, and antibacterial
  • Antitumor, antifungal, and antiviral (correct)
  • Antifungal, antiviral, and antibacterial
  • Antibacterial, antifungal, and antitumor

    • In what year did the US Food and Drug Administration approve mycophenolic acid, and for what purpose?

    <p>1995 as a transplant rejection immunosuppressant</p> Signup and view all the answers

    Who is considered the founder of antibacterial chemotherapy?

    <p>Paul Ehrlich</p> Signup and view all the answers

    What concept did Paul Ehrlich propose related to selective staining of different cell types?

    <p>Zauberkugel (magic bullet)</p> Signup and view all the answers

    What led Paul Ehrlich to contemplate the idea of chemotherapia specifica?

    <p>Selective staining of different cell types</p> Signup and view all the answers

    What year did Bartolomeo Gosio first report the discovery of mycophenolic acid?

    <p>1893</p> Signup and view all the answers

    Which naturally occurring secondary metabolites were described using the term 'antibiotic'?

    <p>Bacteria and fungi</p> Signup and view all the answers

    Which German scientist is regarded as the founder of chemotherapy?

    <p>Paul Ehrlich</p> Signup and view all the answers

    What was the key discovery made by Alexander Fleming in 1928?

    <p>The inhibitory effect of Penicillium chrysogenum on Staphylococcus aureus</p> Signup and view all the answers

    Which compound did Ehrlich and his assistant find effective against bacterial strengths and spirilla in 1909?

    <p>Arsphenamine</p> Signup and view all the answers

    Which class of microorganisms do sulfonamides and trimethoprim primarily target?

    <p>Antibacterial</p> Signup and view all the answers

    What significant event in antimicrobial chemotherapy occurred in 1935?

    <p>Discovery of sulfonamides</p> Signup and view all the answers

    How is penicillin classified in terms of its antibiotic family?

    <p>Beta-lactams</p> Signup and view all the answers

    Which mechanism of antibiotic action involves disrupting membrane function?

    <p>Disruption of membrane function</p> Signup and view all the answers

    Which antibiotic was discovered in 1940 and later used unsuccessfully to treat a patient in 1941?

    <p>Penicillin</p> Signup and view all the answers

    What is the classification of tetracyclines in terms of their spectrum of antibacterial activity?

    <p>Broad spectrum</p> Signup and view all the answers

    What specific type of organism is targeted by arsphenamine, marketed for the treatment of syphilis?

    <p>Treponema pallidum</p> Signup and view all the answers

    When did penicillin become available to the public, and its chemical structure discovered?

    <p>1945</p> Signup and view all the answers

    What is the primary function of peptidoglycan layer in bacterial cell wall?

    <p>To maintain cell shape and provide structural support</p> Signup and view all the answers

    What is the effect of β-lactam antibiotics on bacterial cell wall synthesis?

    <p>Prevention of final cross-linking and weakening of cell wall</p> Signup and view all the answers

    What is the function of penicillin-binding proteins (PBPs) in bacterial cells?

    <p>To form and remodel the cell wall during growth and division</p> Signup and view all the answers

    Why are β-lactam antibiotics more effective against G+ bacteria?

    <p>G+ bacteria have thicker peptidoglycan layers and higher osmotic pressure</p> Signup and view all the answers

    What is the result of β-lactam antibiotics binding to PBPs?

    <p>Prevention of final cross-linking and weakening of cell wall</p> Signup and view all the answers

    What is the characteristic of β-lactam antibiotics against growing cells?

    <p>Bactericidal, effective against growing cells</p> Signup and view all the answers

    What is the mechanism by which β-lactam antibiotics weaken the cell wall?

    <p>Inhibition of cross-linking and weakening of cell wall</p> Signup and view all the answers

    What is the effect of β-lactam antibiotics on autolysins?

    <p>Activation of autolysins and promotion of cell lysis</p> Signup and view all the answers

    What is the characteristic of peptidoglycan layer in G- bacteria?

    <p>Thinner layer, lower osmotic pressure</p> Signup and view all the answers

    What is the role of glucosidic linkage in peptidoglycan layer?

    <p>Connection of sugars to form peptidoglycan backbone</p> Signup and view all the answers

    Which type of microorganisms are nitroimidazoles effective against?

    <p>Anaerobes and microaerophiles</p> Signup and view all the answers

    What is the mechanism of action of nitroimidazoles?

    <p>Inhibiting DNA repair enzyme</p> Signup and view all the answers

    Which enzyme is inhibited by fluoroquinolones?

    <p>Both A and B</p> Signup and view all the answers

    What is the effect of sulfonamides on bacterial cells?

    <p>Bacteriostatic</p> Signup and view all the answers

    Which enzyme is inhibited by trimethoprim?

    <p>Dihydrofolate reductase</p> Signup and view all the answers

    Why are sulfonamides and trimethoprim selectively toxic to bacteria?

    <p>Bacteria must synthesize folic acid</p> Signup and view all the answers

    What is the mechanism of action of sulfonamides?

    <p>Competitively inhibiting dihydropteroate synthase</p> Signup and view all the answers

    Which type of bacteria are fluoroquinolones primarily active against?

    <p>G- bacteria</p> Signup and view all the answers

    What is the effect of nitroimidazoles on DNA?

    <p>Extensive DNA strand breakage</p> Signup and view all the answers

    What is the result of the combination of sulfonamides and trimethoprim?

    <p>Sequential blockade of folic acid synthesis</p> Signup and view all the answers

    What is the outcome of bacterial division in the presence of preformed folic acid?

    <p>Progressive exhaustion and inhibition of growth</p> Signup and view all the answers

    Which of the following antibiotics affects the 30S ribosome?

    <p>Tetracyclines</p> Signup and view all the answers

    What is the mechanism of action of tetracyclines in protein synthesis?

    <p>Inhibiting the binding of aminoacyl tRNA to the recognition site</p> Signup and view all the answers

    What is the characteristic of aminoglycosides in terms of their effect on bacterial cells?

    <p>Bactericidal</p> Signup and view all the answers

    Which of the following antibiotics is particularly active against G- bacteria, mycobacteria, and some mycoplasmas?

    <p>Aminoglycosides</p> Signup and view all the answers

    What is the mechanism of action of chloramphenicol in protein synthesis?

    <p>Inhibiting the peptidyl transferase reaction</p> Signup and view all the answers

    Which of the following antibiotics is broad-spectrum and bacteriostatic?

    <p>Chloramphenicol</p> Signup and view all the answers

    What is the characteristic of macrolides in terms of their spectrum of activity?

    <p>Particularly active against G+ bacteria</p> Signup and view all the answers

    What is the mechanism of action of lincosamides in protein synthesis?

    <p>Inhibiting the peptidyl transferase reaction</p> Signup and view all the answers

    What is the characteristic of anaerobes in relation to aminoglycosides?

    <p>Resistant to aminoglycosides</p> Signup and view all the answers

    Which mechanism of antimicrobial resistance involves the modification of antimicrobial targets, preventing access to the target?

    <p>Target modification</p> Signup and view all the answers

    What is the primary difference between intrinsic and acquired resistance?

    <p>Intrinsic resistance is related to the general physiology of an organism, while acquired resistance is due to mutation or gene transfer</p> Signup and view all the answers

    What is the primary concern associated with the overreliance on antibiotics?

    <p>The emergence of antimicrobial resistance</p> Signup and view all the answers

    What is the mechanism of antimicrobial resistance that involves the development of an alternate metabolic pathway that bypasses the reaction inhibited by the drug?

    <p>Alternate metabolic pathway</p> Signup and view all the answers

    Which of the following types of antimicrobial resistance is often structural or biochemical in nature?

    <p>Intrinsic resistance</p> Signup and view all the answers

    What is the definition of antimicrobial resistance?

    <p>The ability of a microorganism to withstand the effect of a normally active concentration of an antimicrobial agent</p> Signup and view all the answers

    What is the result of the modification of antimicrobial agents by enzymes in bacterial cells?

    <p>The antimicrobial agent is inactivated</p> Signup and view all the answers

    What was the significance of the discovery of penicillin in 1938?

    <p>It marked the beginning of a new era of medicine and helped to develop new antibiotics</p> Signup and view all the answers

    What has been the outcome of the introduction of new classes or modifications of older classes of antimicrobials over the past 7 decades?

    <p>The emergence of new bacterial resistance mechanisms</p> Signup and view all the answers

    What is the primary mechanism of antimicrobial resistance in bacteria that lack a cell wall, such as mycoplasma?

    <p>Lack of cell wall penetration</p> Signup and view all the answers

    What was the concern expressed by A. Fleming in his Nobel Prize acceptance speech in 1945?

    <p>The improper use of penicillin and the ease of resistance with insufficient treatment dosage</p> Signup and view all the answers

    What is the current state of antibiotics in terms of their effectiveness against bacteria?

    <p>Antibiotics are effective against a wide range of bacteria, but antimicrobial resistance is emerging</p> Signup and view all the answers

    What is the primary mechanism of antibiotic resistance in clinical isolates?

    <p>Acquisition of extrachromosomal resistance genes</p> Signup and view all the answers

    What is the term used to describe the transfer of DNA from one organism to another, resulting in a permanent change in the recipient's genetic composition?

    <p>Horizontal gene transfer</p> Signup and view all the answers

    What is the result of a single-step mutation in the presence of antibiotics?

    <p>A dramatic increase in resistance</p> Signup and view all the answers

    What is the term used to describe the collection of mobile genetic elements that can move around within or between genomes?

    <p>Mobilome</p> Signup and view all the answers

    What is the purpose of using antibiotics in combination to overcome the possibility of mutation to resistance?

    <p>To decrease the chance of mutation to resistance</p> Signup and view all the answers

    What is the result of the process of transformation in bacteria?

    <p>The uptake of naked DNA present in the environment</p> Signup and view all the answers

    What is the characteristic of multistep mutations in terms of antibiotic resistance?

    <p>They result in a gradual increase in resistance</p> Signup and view all the answers

    What is the significance of the rate of mutation in antibiotic resistance?

    <p>It is characteristic of each antibiotic</p> Signup and view all the answers

    What is the primary source of antimicrobial resistance genes in human pathogens?

    <p>Environmental non-pathogenic bacteria</p> Signup and view all the answers

    How do non-pathogenic bacteria of animal origin acquire resistance genes for human pathogenic bacteria?

    <p>All of the above</p> Signup and view all the answers

    What is a major factor contributing to the lack of development of new antibiotics?

    <p>Economic hurdles</p> Signup and view all the answers

    What is the main reason for the over-reliance on antibiotics?

    <p>Over-prescription of antibiotics</p> Signup and view all the answers

    What is the primary mechanism by which resistance genes can spread quickly among bacteria?

    <p>Horizontal gene transfer</p> Signup and view all the answers

    What is the main consequence of the lack of regulation in antibiotic use in agriculture and environment?

    <p>Increased emergence of antibiotic-resistant bacteria</p> Signup and view all the answers

    What is the primary goal of establishing effective surveillance systems for collecting data on resistant organisms?

    <p>To control the spread of antibiotic-resistant bacteria</p> Signup and view all the answers

    What is the main reason why many pharmaceutical companies have redirected their attention towards more profitable drugs?

    <p>The development of new antibiotics is time-consuming and expensive</p> Signup and view all the answers

    What is the outcome of the process of transformation in bacteria?

    <p>Production of novel forms of existing genes</p> Signup and view all the answers

    What is the primary function of plasmids in bacteria?

    <p>Carry genes that provide selective advantages to the host bacteria</p> Signup and view all the answers

    What is the role of the sex pilus in conjugation?

    <p>Attachment of the donor bacterium to the recipient bacterium</p> Signup and view all the answers

    What is the significance of transduction in the spread of antimicrobial resistance?

    <p>It has been underestimated in its importance</p> Signup and view all the answers

    What is the outcome of the conjugation process in bacteria?

    <p>The recipient bacterium becomes a potential donor</p> Signup and view all the answers

    What is the best-known example of the emergence of antimicrobial resistance due to transformation?

    <p>The development of penicillin resistance in streptococcus pneumonia</p> Signup and view all the answers

    What is the main role of plasmids and conjugation in the global antimicrobial resistance gene in bacteria?

    <p>They are the major players in the global antimicrobial resistance gene in bacteria</p> Signup and view all the answers

    What is the term used to describe the quantitative ability of an agent to cause disease?

    <p>Virulence</p> Signup and view all the answers

    What is the term used to describe the mechanisms that lead to the development of signs and symptoms of disease?

    <p>Pathogenesis</p> Signup and view all the answers

    What is the term used to describe the ability of bacteria to adhere to host cells?

    <p>Adherence</p> Signup and view all the answers

    What is the term used to describe the process by which bacteria enter host cells and tissues?

    <p>Invasion</p> Signup and view all the answers

    What is the term used to describe the characteristics of bacteria that are pathogens?

    <p>Virulence factors</p> Signup and view all the answers

    What is the term used to describe the molecules that allow bacteria to adhere to host cells?

    <p>Adhesins</p> Signup and view all the answers

    What is the term used to describe the process by which bacteria multiply within host cells?

    <p>Colonization</p> Signup and view all the answers

    What is the term used to describe the ability of bacteria to evade or survive the host's immune system?

    <p>Immunoevasion</p> Signup and view all the answers

    What is the term used to describe the dynamic relationship between the host and the pathogen?

    <p>Host-pathogen interaction</p> Signup and view all the answers

    What is the term used to describe the factors that contribute to the development of disease?

    <p>Virulence factors</p> Signup and view all the answers

    What is the term for the clinical manifestation of the infectious process?

    <p>Infectious disease</p> Signup and view all the answers

    What is the term for the multiplication of an infectious agent within the body?

    <p>Infection</p> Signup and view all the answers

    What is the term for the presence and multiplication of bacteria in the blood?

    <p>Septicemia</p> Signup and view all the answers

    What is the term for the ability of an infectious agent to cause disease?

    <p>Pathogenicity</p> Signup and view all the answers

    What is the term for the microorganism capable of causing disease?

    <p>Pathogen</p> Signup and view all the answers

    How can an animal get infected with exogenous infection?

    <p>All of the above</p> Signup and view all the answers

    What is the term for the infectious agent that is part of the normal microbiota of the gastrointestinal tract, skin, and so on?

    <p>Commensal</p> Signup and view all the answers

    What is the term for the portals of entry of pathogens into the body?

    <p>All of the above</p> Signup and view all the answers

    What is the term for the generalisation of the infection or later it becomes systemic?

    <p>Bacteremia</p> Signup and view all the answers

    What is the term for the multiplication of an infectious agent within the body that does not lead to clinical signs?

    <p>Infection</p> Signup and view all the answers

    What is the term used to describe the relationship between organisms where one benefits and the other is not affected?

    <p>Commensalism</p> Signup and view all the answers

    What is the term used to describe the normal microbiota that usually do not produce disease but achieve balance that ensures survival, growth, and propagation of bacteria and the host?

    <p>Normal microbiota</p> Signup and view all the answers

    Who proposed a series of postulates that have been applied broadly to many bacterial species with particular diseases?

    <p>Robert Koch</p> Signup and view all the answers

    What is the main limitation of Koch's postulates?

    <p>They do not apply to all microorganisms</p> Signup and view all the answers

    What is the term used to describe the reciprocally beneficial associations of organisms?

    <p>Mutualism</p> Signup and view all the answers

    What is the term used to describe the normal flora that inhabit inanimate environments shared with animals?

    <p>Saprophytes</p> Signup and view all the answers

    Why is it difficult to show that a specific bacterial species is the cause of a particular disease?

    <p>Because the bacteria is not present in all cases of the disease</p> Signup and view all the answers

    What is the term used to describe the associations between organisms where one organism benefits and the other is harmed?

    <p>Parasitism</p> Signup and view all the answers

    What is the main strategy of microbiology for identifying bacteria that cause disease?

    <p>Koch's postulates</p> Signup and view all the answers

    What is the limitation of Koch's postulates in relation to mycobacterium leprae?

    <p>It cannot be grown in vitro</p> Signup and view all the answers

    What is the primary function of bacteria in the animal gut?

    <p>To synthesize vitamins and ferment complex carbohydrates</p> Signup and view all the answers

    What is the term for an aggregate of interactive bacteria attached to a solid surface or to each other and encased in an exopolysaccharide matrix?

    <p>Biofilm</p> Signup and view all the answers

    What is the name of the process by which bacteria inhibit the growth of potentially pathogenic bacteria?

    <p>Competitive exclusion</p> Signup and view all the answers

    What is the term for microorganisms that constantly and consistently inhabit the animal body?

    <p>Microbiota</p> Signup and view all the answers

    What is the role of Lactobacillus in the gut?

    <p>To ferment lactose and other sugars to lactic acid</p> Signup and view all the answers

    What is the name of the process by which bacteria evade the host's immune system?

    <p>Evasion</p> Signup and view all the answers

    What is the term for a microorganism that lives in a symbiotic relationship with its host, providing a benefit to the host?

    <p>Commensal</p> Signup and view all the answers

    What is the primary function of bacteria in the formation of biofilms?

    <p>To aid in the formation of biofilms</p> Signup and view all the answers

    What is the term for the assemblage of microorganisms that constantly and consistently inhabit the animal body?

    <p>Microflora</p> Signup and view all the answers

    What is the term for the process by which bacteria attach to surfaces?

    <p>Adherence</p> Signup and view all the answers

    What characteristic allows some bacteria to avoid phagocytosis?

    <p>Possession of a capsule</p> Signup and view all the answers

    Which bacterial component is responsible for the toxic effects associated with endotoxins?

    <p>Lipid-A portion</p> Signup and view all the answers

    What is a common consequence on the host of endotoxin release?

    <p>Blood coagulation</p> Signup and view all the answers

    Which bacteria produce the exotoxin that inhibits acetylcholine vesicle release?

    <p>Clostridium botulinum</p> Signup and view all the answers

    Which exotoxin prevents the release of glycine and GABA?

    <p>Tetanospasmin</p> Signup and view all the answers

    How do exotoxins primarily differ from endotoxins?

    <p>They are heat-sensitive soluble proteins</p> Signup and view all the answers

    What strategy do bacteria use to mimic host molecules and evade the immune system?

    <p>Modulating cell surfaces</p> Signup and view all the answers

    What type of virulence factor is produced exclusively by Gram-negative bacteria?

    <p>Endotoxins</p> Signup and view all the answers

    Which type of bacteria can multiply inside phagocytes?

    <p>Capsule-forming bacteria</p> Signup and view all the answers

    What is the mechanism of action for decarboxylase produced by some bacteria?

    <p>Production of toxic metabolites</p> Signup and view all the answers

    Study Notes

    History of Antimicrobial Chemotherapy

    • The term "antibiotic" originated from the word "antibiose" coined by Paul Vuillemin in 1890, describing the antagonist action between microorganisms.
    • Mycophenolic acid, the first antibiotic discovered from nature, was first reported by Bartolomeo Gosio in 1893 and isolated from Penicillium brevicompactum.
    • Mycophenolic acid showed bacteriostatic, anti-viral, anti-fungal, and anti-tumor properties, but remained undiscovered until its rediscovery in 1913 in the USA.
    • Paul Ehrlich, a German physician and scientist, founded antibacterial chemotherapy and proposed the concept of the "magic bullet" (Zauberkugel).
    • Ehrlich and his group synthesized and tested compounds from arselenic acid against bacterial strains, leading to the development of Arsphenamine (Salvarsan) in 1909.
    • Arsphenamine was the first man-made antibacterial agent, effective against syphilis, and remained the most effective treatment until penicillin became available in the 1940s.

    Discovery of Penicillin

    • Alexander Fleming discovered penicillin in 1928 when a Staphylococcus aureus colony contaminated with Penicillium chrysogenum showed lysis.
    • Fleming attempted to isolate and purify penicillin but was unsuccessful until 1940.
    • Penicillin was first used for treatment in 1941, but the patient died, and the drug supply ran out.
    • Penicillin became available to the public in 1945, and its structure was discovered, classifying it as the first member of the beta-lactam family of antibiotics.

    Development of Antimicrobial Chemotherapy

    • The current era of antimicrobial chemotherapy began in 1935 with the discovery of sulfonamides.
    • Notable discoveries in the following years:
      • 1939: First polypeptide antibiotic discovered
      • 1943: First aminoglycoside antibiotic discovered (streptomycin)
      • 1945: Tetracyclines discovered
      • 1947: Chloramphenicol discovered
      • 1950s: Azomycin, Metronidazole, macrolides, glycopeptides, and streptogramins discovered

    Classification of Antimicrobial Drugs

    • Classification based on spectrum of activity against class of microorganism:
      • Antibacterial (e.g., penicillin)
      • Antifungal
      • Antiprotozoal (e.g., sulfanomides, trimadoprime)
    • Antibacterial activity:
      • Narrow spectrum (e.g., bacitracin, vacomycin; polymyxin)
      • Broad spectrum (e.g., tetracyclines)
    • Pharmacodynamic activity: antibacterial action depends on concentration and time.
    • Mechanism of action depends on drug class:
      • Inhibition of protein synthesis
      • Inhibition of nucleic acid synthesis
      • Inhibition of cell wall synthesis
      • Disruption of membrane function
      • Block pathways and inhibit metabolism

    Inhibition of Cell Wall Synthesis

    • Antibiotics that interfere with cell wall synthesis include β-lactam antibiotics (penicillins, cephalosporins), bacitracin, and vancomycin.

    Bacterial Cell Wall

    • The bacterial cell wall is a thick envelope that gives shape to the cell and distinguishes it from mammalian cells.
    • In Gram-positive (G+) bacteria, the cell wall is thick, consisting of a layer of peptidoglycans that provides rigidity and maintains high internal osmotic pressure.
    • In Gram-negative (G-) bacteria, the layer is thinner, resulting in lower osmotic pressure.

    Peptidoglycan Layer

    • The peptidoglycan layer consists of a polysaccharide chain made up of a repeating disaccharide backbone of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).
    • The sugars are connected through a glucosidic linkage, and a tetrapeptide is attached to N-acetylmuramic acid, with peptide interbridges connecting one peptide to another.
    • The disaccharide backbone is cross-linked both within and between layers, giving the cell wall remarkable strength.

    β-Lactam Antibiotics

    • β-Lactam antibiotics bind to penicillin-binding proteins (PBPs), many of which are transpeptidase enzymes responsible for cell wall formation and remodeling during growth and division.
    • Different penicillin-binding proteins have different affinities for drugs, explaining the variation in the spectrum of action of different β-lactam antibiotics.
    • By binding to PBPs, β-lactam antibiotics prevent the final cross-linking in the cell wall, inhibiting cell division and creating weak points.

    Effects of β-Lactam Antibiotics

    • β-Lactam antibiotics decrease normal inhibition of autolysins and block peptidoglycan synthesis, weakening the cell wall and promoting cell lysis.
    • They are active against growing cells, bactericidal, and have greater activity against G+ bacteria due to the higher quantity of peptidoglycan and high osmotic pressure.
    • The activity of β-lactam antibiotics can be expanded by combining them with β-lactamase-inhibiting drugs, such as clavulanic acid and sulbactam, to neutralize enzymes that might otherwise inactivate them.

    Nitroimidazoles

    • Possess antiprotozoal and antibacterial properties
    • Affect only anaerobes and microaerophiles, which reduce the drug
    • Reduced products cause DNA strand breakage by inhibiting DNA repair enzyme - DNase 1 or forming complexes with nucleotide bases
    • Bactericidal against anaerobic G- and many G+ bacteria, and active against protozoa such as Trichomonas fetus, Giardia lamblia, and Histomonas meleagridis

    Fluoroquinolones

    • Active against G- bacteria
    • Selectively inhibit bacterial DNA synthesis by inhibiting DNA gyrase (topoisomerase II) and DNA topoisomerase IV
    • DNA gyrase is involved in packing DNA into bacterial cells, while topoisomerase IV is involved in relaxing supercoiled DNA
    • Bactericidal, with newer fluoroquinolones being broader spectrum and active against some G+ bacteria, including mycobacteria, mycoplasmas, and rickettsia

    Sulfonamides and Trimethoprim

    • Synthetic drugs with antibacterial and antiprotozoan properties
    • Interfere with biosynthesis of folic acid, necessary for nucleic acid production in bacteria
    • Sulfonamides competitively inhibit the enzyme dihydropteroate synthase and block folic acid synthesis
    • Active against G+ and G- bacteria and protozoa, with bacteriostatic effects
    • Trimethoprim inhibits the enzyme dihydrofolate reductase, producing a sequential blockade of folic acid synthesis
    • Bacteriostatic, with selective toxicity due to mammalian cells absorbing folic acid from the intestine, while bacteria must synthesize it

    Inhibition of Protein Synthesis

    • Examples include tetracyclines, aminoglycosides, chloramphenicol, lincosamides, and macrolides
    • Can be divided into those affecting the 30S ribosome (tetracyclines, aminoglycosides) and those affecting the 50S ribosome (chloramphenicol, macrolides, lincosamides)

    Tetracyclines

    • Interfere with protein synthesis by inhibiting the binding of aminoacyl tRNA to the recognition site
    • Bacteriostatic, with broad-spectrum activity against G+, G-, including rickettsia, chlamydia, some mycoplasmas, and protozoa (such as Theileria)

    Aminoglycosides

    • Complex effects in the bacterial cell, including:
      • Binding to a specific receptor protein in the 30S ribosomal subunit, distorting the anti-code interaction at recognition site
      • Causing misreading of the genetic code, leading to faulty proteins being produced
      • Binding to "initiating" ribosomes, preventing the formation of 70S ribosomes
      • Inhibiting the elongation reaction of protein synthesis
    • Bactericidal, particularly active against G- bacteria, mycobacteria, and some mycoplasmas
    • Anaerobes are resistant, often combined with β-lactams

    Chloramphenicol and Macrolides

    • Chloramphenicol is broad-spectrum, bacteriostatic, and binds the 50S ribosome, distorting the region and inhibiting the peptidyl transferase reaction
    • Active against G+ and G- bacteria, including chlamydia, rickettsia, and some mycoplasmas
    • Macrolides are bacteriostatic, particularly active against G+ bacteria and Mycoplasma
    • Mechanism of action is the same as for chloramphenicol and lincosamides

    Antimicrobial Resistance

    • Prior to the commercialization of antibiotics, main causes of death were pneumonia, flu, tuberculosis, and GI infections.
    • During WWI, infectious diseases caused more deaths than battle wounds.
    • The discovery of penicillin in 1938 marked a new era of medicine, helping to develop new antibiotics and changing the entire drug discovery process.

    Emergence of Antimicrobial Resistance

    • Overreliance on antibiotics led to the emergence of antimicrobial resistance, which was not unexpected.
    • A. Fleming predicted the emergence of resistance and expressed concern about the improper use of penicillin in his Nobel Prize acceptance speech in 1945.

    Resistance Mechanisms

    • Antimicrobial resistance is defined as the ability of a microorganism to withstand the effect of a normally active concentration of an antimicrobial agent.
    • Five major categories of antimicrobial resistance mechanisms:
      • Antimicrobial agent (AMA) is prevented from reaching its target by reducing its penetration into the bacterial cell.
      • AMAs are expelled out of the cell by general or specific efflux pumps.
      • AMAs can be inactivated by modification or degradation.
      • Antimicrobial targets can be modified or protected by another molecule preventing access of antibiotic to its target.
      • Microorganisms can develop alternate pathways that bypass the reaction inhibited by the drug.

    Types of Resistance

    • Intrinsic resistance: chromosomally encoded, relates to the general physiology of an organism, natural to all members of a specific bacterial taxonomic group.
    • Examples of intrinsic resistance: G- bacteria are resistant to macrolides, aminoglycosides have reduced activity in anaerobes, G+ bacteria are resistant to polymyxins.
    • Acquired (extrinsic) resistance: mutation in a resident gene, transfer of genetic material (via plasmids, bacteriophages, transposons).
    • Acquired resistance can result from the mutation of genes involved in normal physiological processes and cellular structures, or from the acquisition of foreign resistance genes.

    Mutation and Resistance

    • Gene mutations occur continuously at a relatively low frequency (10-8-10-9).
    • Mutation-based resistance is often a gradual stepwise process where a transferable resistance is often high-level, all-or-none resistance.
    • Mutations can lead to other changes that leave the cell at a disadvantage, and in the absence of antibiotic selection, these mutants may gradually be lost.

    Horizontal Gene Transfer

    • Foreign DNA can be acquired by bacteria in three different ways: transformation, transduction, and conjugation.
    • Mobilome: all mobile genetic elements that can move around within or between genomes in a cell (plasmids, transposons, bacteriophages, self-splicing molecular parasites).
    • DNA can be transferred from one organism to another through horizontal gene transfer, permanently changing the recipient's genetic composition.

    Horizontal Gene Transfer

    • Transformation: a process by which DNA is taken up from the environment by bacteria, resulting in the emergence of new forms of existing genes
    • Example: emergence of penicillin resistance in Streptococcus pneumoniae through the development of novel penicillin-binding proteins

    Transduction

    • Process by which bacteriophages (bacterial viruses) transfer resistant genes between bacteria
    • Example: transfer of β-lactamase genes from penicillin-resistant to previously penicillin-susceptible Staphylococci

    Conjugation

    • Plasmids and conjugation are major players in the global spread of antimicrobial resistance genes in bacteria
    • During conjugation, a donor bacterium synthesizes a sex pilus, which attaches to a recipient bacterium, resulting in the transfer of plasmid genes
    • Conjugation can occur between different species and families, allowing for the spread of antimicrobial resistance genes

    Origin of Resistance Genes

    • Resistance genes originated long before the introduction of therapeutic antimicrobials into medicine
    • Antibiotic-producing microorganisms developed resistance mechanisms to protect themselves from their own antibiotics
    • Evidence suggests that resistance genes in human pathogens originated from environmental, non-pathogenic bacteria via horizontal gene exchange

    Factors Contributing to Antibiotic Resistance

    • Lack of regulation in antibiotic use, particularly in agriculture and the environment
    • Use of antibiotics as growth promoters in agriculture
    • Over-prescription of antibiotics, including for viral infections
    • Economic hurdles that have stalled the development of new antibiotics by pharmaceutical industries

    Controlling Antimicrobial Resistance

    • Establishing effective surveillance systems for collecting data on resistant organisms
    • Monitoring the supply and use of antimicrobial drugs
    • Enforcing strict adherence to recommended therapeutic doses and drug withdrawal periods
    • Not using antimicrobial agents for growth promotion
    • Greater reliance on better hygiene, disinfection, and vaccination for prevention and control of infectious diseases

    Bacteria and Ecological Associations with Animals

    • Bacteria can be classified into three categories based on their ecological associations with animals: parasites, commensals, and saprophytes.
    • Parasites live in permanent association with an animal host and at the expense of the host.
    • Commensals are parasites that cause no discernible harm to the host.
    • Saprophytes normally inhabit inanimate environments shared with animals.

    Identifying Bacteria that Cause Disease

    • Robert Koch proposed a series of postulates in 1884 to determine whether a specific bacterial species causes a particular disease.
    • Koch's postulates:
      • The suspected agent is present in all cases of the disease.
      • The agent is isolated from the disease and propagated serially in pure culture, apart from its natural host.
      • Upon introduction into an experimental host, the isolate produces the original disease.
      • The agent can be reisolated from this experimental infection.
    • Many microorganisms do not meet the criteria of Koch's postulates but have been shown to cause disease.

    Infection and Infectious Disease

    • Infection refers to the multiplication of an infectious agent within the body.
    • Infectious agents can be pathogenic microorganisms such as bacteria, viruses, parasites, or fungi.
    • Infection does not necessarily imply disease, as it may not lead to clinical signs or impairment of normal function.
    • Infectious disease refers to the clinical manifestation of the infectious process.
    • Infections can be exogenous (occurring after direct or indirect transmission from an infected animal or the environment) or endogenous (caused by commensal bacteria when an animal is subjected to stressful environmental factors).

    Transmission of Infection

    • Modes of transmission:
      • Contact: direct or indirect transmission from one animal to another.
      • Vectors: mechanical (insects) or passive (fomites).
      • Iatrogenic: after medical activity.
      • Vertical: from mother to baby.
      • By ingestion, inhalation, or inoculation.

    Portals of Entry

    • Skin provides a protection barrier for pathogens, which must overcome these barriers.
    • Most frequent portals of entry:
      • Damaged skin (cuts, burns, and other injuries).
      • Damaged mucous membranes (upper, lower respiratory tract, gastrointestinal tract, genital, urinary tracts, conjunctiva).
      • Injuries (including surgical sites).
      • Teats, umbilicus.

    Definitions

    • Bacteremia: presence of bacteria in the blood (transient).
    • Septicemia: presence and multiplication of bacteria in the blood (usually leads to sepsis).
    • Sepsis: the body's extreme response to an infection that damages its own tissues.
    • Pathogen: a microorganism capable of causing disease.
    • Virulence: the quantitative ability of an agent to cause disease.
    • Virulence factors: toxins, enzymes, and other bacteria-produced molecules and substances that alter normal growth.

    Pathogenesis of Bacterial Infection

    • Characteristics of pathogenic bacteria:
      • Transmissibility.
      • Adherence to host cells.
      • Persistence.
      • Invasion of host cells and tissues.
      • Toxigenicity.
      • Ability to evade or survive the host's immune system.

    Adherence Factors

    • Adhesins: specific surface molecules that interact with host cells (receptors).
    • Examples: pili, fimbriae, lipoteichoic acid.

    Invasion Factors

    • Invasion: the entry of bacteria into host cells and further spread into host tissues.
    • Invasion may be facilitated through breakdown of host tissues by different enzymes.
    • Host cells play an active role in the invasion process.

    Immune Evasion Strategies

    • Bacteria employ tactics to avoid or inactivate host defenses, ensuring their survival within a host
    • Tactics include modulating their cell surfaces, releasing proteins to inhibit or degrade host immune factors, and mimicking host molecules
    • Some bacteria can escape phagocytosis by having a capsule, and some can even multiply in phagocytes

    Toxigenicity Factors

    • Toxins are specific virulence factors produced by some bacterial pathogens, in the form of substances poisonous to the host
    • Toxigenicity refers to an organism's ability to make toxins
    • Bacteria can produce:
      • Enzymes (e.g., urease and decarboxylase) that break down certain substances, producing toxic metabolites
      • Exotoxins
      • Endotoxins

    Endotoxins

    • Integral part of gram-negative bacteria
    • Toxicity resides in the lipid-A portion of the lipopolysaccharide molecule
    • Released when bacterial cells are lysed
    • Effects on the host: fever, diarrhea, weakness, blood coagulation

    Exotoxins

    • Heat-sensitive soluble proteins released by living organisms
    • Can be produced by both gram-positive and gram-negative bacteria
    • Incredibly potent and can spread throughout the host body, causing damage distant from the original site of infection
    • Associated with specific diseases, such as:
      • Botulism (produced by Clostridium botulinum)
      • Tetanus (produced by Clostridium tetani)
      • Diphtheria

    Bacterial Biofilms

    • An aggregate of interactive bacteria attached to a solid surface or to each other, encased in an exopolysaccharide matrix
    • Form a slimy coat on solid surfaces, occurring throughout nature
    • Play a critical role in bacterial pathogenesis and environmental quality
    • Can cause equipment damage, product contamination, and aid attachment and survival
    • Protect from phagocytosis, antibodies, and antibiotics
    • Examples: colonization of heart valves, catheter medical devices, and prostheses

    Animal Microflora

    • The assemblage of microorganisms that constantly inhabit the animal body
    • Includes bacteria, fungi, and archaea
    • Majority have no known beneficial or harmful effect on the animal
    • Some have important tasks that are useful for the host
    • Estimated 500-1000 species of bacteria live in the animal gut and a similar number on the skin
    • Bacteria are vital for the maintenance of animal health, synthesizing vitamins, fermenting complex carbohydrates, and converting lactose to lactic acid
    • Presence of bacterial colonies also inhibits the growth of potentially pathogenic bacteria and trains the animal's immune system

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