Proteus, Providencia & Morganella Group: Mod 19 2023-2024 PDF

C L I N I C A L B A C T E R I O L O G Y Proteus, Providencia & Morganella Group: Mod 19 MRS. PAZ RELEVO BACULI, RMT 2023-2024 Proteus mirabilis was first discovered by Gustav Hauser, a German ...

C L I N I C A L B A C T E R I O L O G Y Proteus, Providencia & Morganella Group: Mod 19 MRS. PAZ RELEVO BACULI, RMT 2023-2024 Proteus mirabilis was first discovered by Gustav Hauser, a German  Swarming is a cyclic, multicellular behavior allowing rapid pathologist. He named the genus Proteus, after the character in migration of “rafts” of P. mirabilis cells over solid surfaces. On Homer’s The Odyssey. (Proteus had an uncanny ability to change his contact with a solid surface, P. mirabilis swimmer cells (1 to 2 μm shape and evade being questioned, just like the organism’s ability to in length) differentiate into elongated, hyperflagellated swarmer avoid the host’s immune system.) Proteus mirabilis is a gram-negative, cells (up to 80 μm long), which exhibit increased expression of rod-shaped bacterium and a natural flora of the intestine. virulence factors. (Slide # 4) Proteus Specie Members Urease Test  Proteus vulgaris  Proteus penneri  Proteus mirabilis  Proteus lauseri Urease broth is a differential medium that tests the ability of an organism  Proteus rettgeri  Proteus myxofaciens to produce an exoenzyme, called urease, that hydrolyzes urea to ammonia and carbon dioxide. The broth contains two pH buffers, urea, a  Proteus mirabilis and Proteus vulgaris are the most frequently very small amount of nutrients for the bacteria, and the pH indicator isolated organisms in humans. phenol red. Phenol red turns yellow in an acidic environment and fuchsia in an alkaline environment. If the urea in the broth is degraded and  The first isolates were reported and characterized by Hauser in the ammonia is produced, an alkaline environment is created, and the media late 19th century. turns pink.  Proteus organisms are implicated as serious causes of infections in Many Enterics can hydrolyze urea; however, only a few can degrade urea humans, along with Escherichea, Klebsiella, Enterobacter, and rapidly. These are known as “rapid urease-positive” organisms. Serratia species. Members of the genus Proteus are included among these organisms.  Proteus is found in multiple environmental habitats, including Urea broth is formulated to test for rapid urease-positive organisms. The long-term care facilities and hospitals. restrictive amount of nutrients coupled with the use of pH buffers prevent all but rapid urease-positive organisms from producing enough  Proteus mirabilis is a Gram-negative, facultatively anaerobic, rod- ammonia to turn the phenol red pink. shaped bacterium. It shows swarming motility and urease activity.  Proteus Vulgaris is a chemoheterotrophic bacterium. The size of the individual cells varies from 0.4 to 0.6 micrometers by 1.2 to 2.5 Proteus mirabilis is Escherichia coli is micrometers. P. vulgaris possesses peritrichous flagella, making it rapid urease positive urease negative. actively motile. as evidenced by the pink color of the  P. mirabilis is capable of swarming, a form of multicellular media. behavior in which bacteria differentiate from the short rod typical of members of the family Enterobacteriaceae, termed the swimmer Note: Urease broth can be used to differentiate members of the genus cell, into hyperflagellated elongated bacteria capable of rapid and Proteus (as well as those of Morganella and Providencia) from other coordinated population migration across surfaces, called the Enterics. swarmer cell. There has been considerable debate as to which morphotype predominates during urinary tract infection.  In liquid medium, P. mirabilis exists as a short (1.5 to 2 μm) motile rod with peritrichous flagella typical of members of the family Enterobacteriaceae. When transferred from liquid to an agar surface, the cells undergo striking changes in morphology and physiology, which result in a differentiated morphotype, called a swarmer cell, that is capable of multicellular rapid movement. Soon after encountering the solid surface of the agar, bacteria elongate dramatically due to an inhibition of septation, reaching 10 to 40 μm with minimal increase in cell width. During elongation, DNA replication is not affected, while the synthesis rates of certain proteins, most notably, urease, hemolysin, ZapA, and flagellin, are markedly increased.  Like many bacteria, P. mirabilis uses flagella to swim through liquids and toward chemical gradients P. mirabilis switches between swimming and swarming forms. On the left  In liquid culture, P. mirabilis is short rod shaped and typically is a transmission electron micrograph (TEM) of broth-cultured, possesses a few peritrichous flagella. However, on rich solid vegetative cells displaying peritrichous flagella. On the right is a TEM of media, P. mirabilis differentiates into very long (typically 20-80 μm, differentiated swarm cells. Bundles of flagella are visible although cells longer than 100 μm occur), non-septate polyploid cells with hundreds to thousands of flagella. These swarmer cells move as a population across surfaces. Page 1 of 8  Although the flagella produced by this organism are generally types of samples collected, and the characteristics of the patients similar to flagella produced by other bacteria, there are two examined. unusual characteristics of P. mirabilis flagella.  The wide range of P. mirabilis CAUTI likely reflects differences in a) First, all genes encoding flagellar components, including the class I the population surveyed and the types of samples collected. The flagellar master regulatory genes flhDC, are found within a single highest incidence of P. mirabilis CAUTI occurs in elderly patients 54 kb locus in the chromosome. This is in contrast to most other during long-term catheterization. flagella-producing bacteria, which have flagellar operons in (CAUTI - catheter-associated urinary tract infections) disparate loci. b) Second, P. mirabilis encodes two flagellins, FlaA and FlaB (also Antigenic Structures known as FliC1 and FliC2, respectively), which comprise the whip structure of the flagellum.  The bacilli possess thermostable, ‘O’ (somatic) and thermostable ‘H’ (flagellar) antigens, based upon which several serotypes have been  This organism is more common in complicated urinary tract recognized. infections (such as patients with spinal cord injury or anatomical abnormality) and especially contributes to catheter-associated UTI  Certain strains of Proteus vulgaris (OX-19, OX-2, and OX-K) (CAUTI). produce O antigens that are shared by some rickettsiae. These Proteus strains are used in an agglutination test (the Weil- Felix test) for serum antibodies produced against rickettsiae of the typhus and spotted fever groups. Virulence Factors  Several virulence factors have been identified and characterized for P. mirabilis. 1 a potent urease that catalyzes formation of ammonia from urea and leads to urinary stone formation 2 a pore-forming hemolysin 3 ZapA metalloprotease which cleaves both immunoglobulin IgG and IgA Fluorescent P. mirabilis bull's-eye colony. Five microliters of a culture of 4 a capsular polysaccharide P. mirabilis HI4320(pBAC001) grown overnight was spotted onto the center of a swarming plate and incubated for 8 h at 37°C. P. 5 four distinct fimbrial types mirabilis(pBAC001) swarmed normally and is fluorescent. Swarmer (C) 6 peritrichous flagella for swimming and swarming motility and swimmer (D) morphotypes expressed GFP. Bacteria from several regions of the bull's-eye colony were sampled and viewed by confocal  The cytoplasmic nickel metalloenzyme urease acts by hydrolyzing microscopy (The green fluorescent protein (GFP) is a protein that urea into ammonia and carbon dioxide. The resulting ammonia is exhibits bright green fluorescence when exposed to light in the blue the preferred nitrogen source for many species of bacteria, and to ultraviolet range.) may be assimilated into biomolecules via glutamine synthetase (GlnA) or glutamate dehydrogenase (GdhA). Short-form swimmer cells isolated from the center of the bull's-eye and  A direct result of urease activity and ammonia generation is an the elongated swarmer cells taken from the leading edge of the increase in local pH. In the urinary tract alkaline pH leads to outermost terrace fluoresced bright green when bacteria were visualized precipitation of calcium and magnesium ions and the formation of by laser-scanning confocal microscopy. Thus, both swimmer and urinary stones composed of magnesium ammonium phosphate elongated swarmer cells can be easily detected by fluorescence (struvite) and calcium phosphate (apatite). microscopy. Struvite (magnesium ammonium phosphate) from urine- taken from filter bags, here after 1-2 hours of drying process P. Mirabilis swarms across sections of latex catheter  Proteus mirabilis infection occurs in the following conditions i.e., Apatite - Calcium phosphate longer duration of catheterization, improper catheter cleaning or Calcium phosphate stones are similar to care, underlying illness, and lack of availability of systemic antibiotics. calcium oxalate stones, but instead of the calcium combining with oxalic acid, it  Proteus mirabilis (indole negative) is the most combines with phosphoric acid. These frequent Proteus species associated with urinary tract infections, kinds of stones are not as common, but are but indole-positive Proteus species like Pr. vulgaris, which are more often found in those who have more often resistant to ampicillin, may also cause urinary tract alkaline urine. infections. These species are often associated with an alkaline urine.  These stones can block urinary flow and cause tissue damage; they Mode of Transmission can also become quite large (> 1 cm2).  Proteus spp. are part of the human intestinal flora and can cause  The precipitated minerals may mix with bacteria adherent to a infection upon leaving this location. urinary catheter, forming a crystalline biofilm and eventually  They may also be transmitted through contaminated catheters blocking urine flow through the catheter. (particularly urinary catheters) or by accidental parenteral inoculation.  Bacteria can become embedded in these stones, which may protect  Incidence: P. mirabilis causes between 1-10% of all urinary tract pathogens from antibiotics or the immune system. infections, varying with the geographic location of the study, the Page 2 of 8  Furthermore, urinary stones can act as a focal point for other species of bacteria to establish UTI.  Urease activity during UTI may be influenced by polymicrobial infection; experimental co-infection of mice with P. mirabilis and urease-positive Providencia stuartii resulted in increased urolithiasis and bacteremia despite similar bacterial loads compared to monospecies infection. Potentially important Proteus-related virulence factors in relation to anatomical disease location and disease. *, immune evasion includes the The role of various virulence factors in the formation of crystalline biofilms production of the ZapA metalloprotease, O-antigens, and flagellin by P. mirabilis on catheter surfaces variation. Concepts of Proteus mirabilis pathogenesis during UTI Pathogenesis of Proteus mirabilis Infection  Adherence - binding catheters, host tissues, and neighboring bacteria may all contribute to disease. Adherence is mediated by chaperone-usher fimbriae and autotransporter adhesins.  Urease - involved in stones, crystalline biofilms, and possibly nutrition or host sensing.  Motility - P. mirabilis swarms across catheters and may ascend to the kidneys using swimming motility. Both forms of motion are mediated by flagella. Chemotaxis proteins allow the bacteria to follow chemical gradients.  Metabolism - likely permits establishment of a nutritional niche, competition with other species, and response to host cues. P. mirabilis bacteria (green) form crystalline biofilms on the surface of  Metal scavenging catheters (Top). Once inside the bladder [0.5–6 hours post-infection - iron and zinc uptake are essential for growth, but are sequestered by (hpi)], this organism can invade into urothelial cells of the bladder. As the host; therefore, specialized proteins are required for bacteria to early as 10–24 hpi, P. mirabilis forms intraluminal clusters that can scavenge these metals. extend the length of the bladder and are associated with urothelial cell destruction [perhaps through the production of toxins (yellow stars) or  Toxins an increase in urine pH] and mineral deposition (purple rods). Host - proteins such as HpmA and Pta may aid in nutrient accessibility, innate immune cells such as neutrophils (blue) are recruited to the site of immune evasion, or provision of surfaces to colonize. infection and can form NETs (neutrophil extracellular traps).  Biofilm formation - Crystalline biofilms readily form on catheters, and bacterial clusters in the bladder may be a biofilm-mediated process.  Immune evasion - this can include antibody and antimicrobial peptide degradation, polymyxin resistance, lipopolysaccharide (LPS) variation, and physical obstruction of phagocytosis  Virulence regulation - required to coordinate all steps of infection.  Type 6 secretion system (T6SS) - involved in self-recognition; unknown role during UTI. Indeed, in vitro co-culture of P. mirabilis and P. stuartii in human urine resulted in enhanced total urease activity compared to either species alone. Due to the prominent role of urease in P. mirabilis virulence, this enzyme is an active target of investigation to identify clinically useful inhibitors. Stages of infection of E. coli Page 3 of 8 Since the ability of P. mirabilis to generate urinary stones and crystalline biofilms is dependent upon alkaline pH, another approach to prevent catheter blockage is to acidify the urine. Similarly, mineral nucleation can be inhibited by reducing mineral concentration in the urine, i.e., by increasing fluid intake. These efforts are aimed at increasing the urinary nucleation pH (the pH at which minerals will precipitate from the urine); a lower nucleation pH A particularly large urolith (A) Reconstructed computed tomography is associated with increased stone formation. (Preliminary results with image, showing the location and relative size of the urate cystolith patients consuming lemon juice are promising, with the result of (indicated by arrows). (B) Photograph of the urate cystolith, showing its increased nucleation pH. However, the effect of such treatments on absolute size. catheter blockage has not yet been reported). Complications from infection with this organism are frequently serious and include bladder and kidney stone formation, encrustation and obstruction of the urinary catheter, acute pyelonephritis, and bacteremia. Indeed, this bacterium has a propensity for colonization of the kidney; in bladder washout studies, P. mirabilis was found in the kidneys more often than Escherichia coli. P. mirabilis is capable of causing symptomatic infections of the urinary tract including cystitis and pyelonephritis and is present in cases of P. mirabilis in urease-induced bladder stone. A, One-quarter bladder of asymptomatic bacteriuria, particularly in the elderly and patients with experimentally-infected mouse (bar, 500 μm). B, Higher magnification of type 2 diabetes. the area indicated in panel A (bar, 100 μm). C, Higher magnification of the area indicated in panel B with individual bacteria visible (bar, 5 μm) These infections can also cause bacteremia and progress to potentially life-threatening urosepsis. Laboratory Diagnosis  Indwelling bladder catheterization is a convenient way to manage  Gram negative, Non-spore-forming rods, Facultative anaerobes, the problems of urinary retention and incontinence that afflict so Urease positive (strong), Oxidase test: Negative, many elderly and disabled people. The catheter, however, forms a Nitrates are reduced to nitrites, Ferments glucose but does not bridge along which bacteria can pass from a contaminated external ferment lactose, Deaminates phenylalanine to phenylpyruvic acid. environment into a vulnerable body cavity. Even with meticulous Gram staining, colony characteristics in culture media and bio- nursing care, all patients undergoing catheterization for longer chemical tests (Indole production, urease production, H2S than a month will develop urinary tract infections. The number of production and more importantly Phenyl pyruvic acid (PDA) when catheterized patients is so large that catheter-associated urinary used in combination are sufficient to identify an isolate tract infections (C-UTI) are the most common infections acquired as Proteus species. (Indole (-); Urease (+); K/K, H2S; PPA (+) in hospitals and other health care facilities.  Proteus organisms are easily recovered through routine laboratory  The obstruction of the flow of urine through the catheter can cultures. Most strains are lactose-negative and demonstrate induce serious complications. Urine either leaks around the outside characteristic swarming motility on agar plates. Any positive of the catheter causing patients to become incontinent or is culture result from an otherwise sterile area should be considered retained in the bladder resulting in painful distension of the an acute infection if clinical signs and symptoms are present. bladder and reflux of urine to the kidneys, which can initiate episodes of pyelonephritis, septicemia, and shock. It has been  UTIs in symptomatic patients have traditionally been defined by suggested that the well-known ability of P. mirabilis to swarm recovering bacteria in large numbers (ie, >100,000 colony-forming rapidly over surfaces may play a role in the pathogenicity of this units [CFUs]/mL) on examination. Bacterial counts of less than species in the catheterized urinary tract. 100,000 CFUs/mL may indicate infection in urine samples, especially if obtained directly from the ureters or renal pelvis, Additionally, P. mirabilis infections can cause the formation of urinary whereas specimens from suprapubic catheters usually have stones (urolithiasis). (Slide #21 & 22); Recurrent urinary tract bacterial counts greater than 100,000 CFUs/mL. However, even infections with a urease-producing organism (mostly Proteus species) small numbers of organisms may be of true clinical significance in results in formation of staghorn calculi in the kidney. symptomatic patients (eg, women with the urethral syndrome). (Urethal syndrome - a group of symptoms (as urinary frequency P. mirabilis is often isolated from the gastrointestinal tract, although and urgency, pain and discomfort in the lower abdominal region, whether it is a commensal, a pathogen, or a transient organism, is and dysuria) that resemble those of a urinary tract infection but for somewhat controversial. which no significant bacteriuria exists) It is thought that the majority of P. mirabilis urinary tract infections (UTI)  The sample used for the isolation and identification of the Proteus result from ascension of bacteria from the gastrointestinal tract while species depends on the nature of the disease/site of infections. others are due to person-to-person transmission, particularly in healthcare settings. This is supported by evidence that some patients  For UTI, midstream urine sample is used, and for pyogenic lesions, with P. mirabilis UTI have the same strain of P. mirabilis in their stool, its the pus aspirate. while others have no P. mirabilis in their stools  Sample should be collected in the sterile container maintaining In addition to urinary tract infection, this species can also cause infection aseptic conditions and should reach laboratory within an hour of in the respiratory tract, eye, ear, nose, skin, throat, burns, and wounds collections. and has been implicated in neonatal meningoencephalitis, empyema, and osteomyelitis  Culture: The choice of the culture media used for the isolation of the etiological agents depend on the nature of the specimen and Symptoms: These include dysuria, increased frequency, urgency, suspected pathogens. suprapubic pain, back pain, small volumes, concentrated appearance, and hematuria. These symptoms may not be present if the patient has an  For pus & urine sample, Blood Agar and MacConkey agar are indwelling catheter. commonly used. Proteus grow on the Blood Agar plate in successive waves to form a thin filmy layer of concentric circles If the patient is febrile, this could be a sign of bacteremia and impending ( swarming). Proteus do not swarm in the MacConkey agar sepsis. medium and form smooth, pale or colorless (NLF) colonies. Page 4 of 8  This has been known as the Dienes line (after Louie Dienes, who described the phenomenon in 1946), and is used to distinguish clinical isolates. What we have here is recognition of self and non-self. The Proteus sp - Nitrate mechanism involved remains somewhat murky and little progress has Reduction Test Positive been made in identifying possible secreted molecules. But there is much hope because this topic is being studied in eamest. Proteus – Oxidase Test Negative Proteus sp. – Positive Principle of Dienes Phenomenon: H2S When two different strains of Proteus species inoculated at different places of some non-inhibitory medium (blood agar), swarming of the two strains remains separated by a narrow visible furrow. However, in case of two identical strains of Proteus, swarming of two colonies combines without signs of demarcation. Such condition is called Dienes phenomenon. Dienes test showing three different strains, A, B, and C. Note the absence of Dienes lines between identical strains A and A, B and B, Proteus sp. – PDA Test and C and C, respectively. (+) Likewise, note the distinct lines of demarcation between strains A, B, and C. Morphology and Culture Characteristics of Proteus Vulgaris Swarming properties of Proteus presents problems in the diagnostic laboratory when mixed growth is present in which Proteus is one of the isolate. Several methods have been used to inhibit swarming. These are 1) Increasing the concentration of agar in the medium, raising it to 6% instead of 1-2%. 2) Incorporation of chloral hydrate (1:500), sodium azide (1:500), boric acid (1:1000) in the medium 3) Using Cysteine Lactose Electrolyte Deficient (CLED) as a sole medium instead of MacConkey Agar and Blood Agar for the processing of urine samples. 4) Addition of Teepol (a surface active agent) which is present in Teepol Lactose agar medium. 5) The addition of growth inhibitors like sulphonamides to the medium. 6) The presence of Bile salts in the medium, present in MacConkey agar or DCA medium. Proteus (+) Salmonella enterica, Proteus mirabilis & Escherichia coli on Deoxycholate Citrate Agar Also known for a long time is that if you start two colonies of P. mirabilis on a single plate, you can get two different outcomes depending on their identity. If both colonies are from the same clone, the swarms will simply make contact and melt together. Swarms from different strains, on the other hand, make a visible boundary in the form of a cell-free zone. Page 5 of 8  Culture Characteristis of Poteus vulgaris Treatment Cultural NA medium MAC BAP EMB  Treatment Uncomplicated UTIs in women can be treated on an characteristics medium medium medium outpatient basis with an oral quinolone for 3 days or Shape Irreg due to circular Irreg due to circular trimethoprim/sulfamethoxazole (TMP/SMZ) for 3 days. swarming swarming  Complicated UTIs in men and women can be treated with a 10- to Size 1-2mm 2-3mm 1-2mm 2-3mm 21-day course of oral therapy (in the same manner as for Elevation effuse Low convex effuse effuse hospitalized patients) as long as the follow-up is adequate Surface glistening smooth glistening glistening Color Greyish Colorless / Greyish colorless Prevention white pale colored white Structure translucent transparent Translucent transparent  Vaccination - opaque Hemolysis -------- -------- γ-hemolysis -------- Providencia Specie Providencia stuartii Providencia rettgeri colonies on Endo agar  The genus Providencia consists of five species: P. alcalifaciens, P. heimbachae, P. rettgeri, P. rustigianii, and P. stuartii.  Lactose (-), PAD (+), H2S (-), Motile  P. rettgeri is the only species that is Urease (+) - it is associated with nosocomial infections of the urinary tract and skin. - UTI is common in patients with predisposing urological problem. - Skin infection is common among burn patients. P. vulgaris demonstrating Proteus vulgaris on EMB  P. stuartii - associated with UTI in those with indwelling urinary swarming behavior on DNase catheters. agar. - P. stuartii is the most common of the 5 species found in the genus Providencia. - Providencia stuartii is the most common Providencia species capable of causing human infections. - Providencia stuartii is an opportunistic pathogen seen in patients with severe burns or long-term indwelling urinary catheters. This puts elderly individuals at a greater risk for P. stuartii infections. - P. stuartii can be isolated from urine (most common), stool, and blood, as well as from sputum, skin, and wound cultures. - Upon physical examination, P stuartii bloodstream infection is associated with fever, tachycardia, and hypotension. - In animals P. stuartii infections can cause neonatal diarrhea in dairy Proteus on EMB cows.  Both species are often resistant to antibiotic therapy. The bacilli possess thermostable, ‘O’ (somatic) and thermostable ‘H’ (flagellar) antigens, based upon which several serotypes have been recognized. Certain strains of Proteus vulgaris (OX-19, OX-2, and OX-K) produce O antigens that are shared by some rickettsiae. These Proteus strains are used in an agglutination test (the Weil-Felix test) for serum antibodies produced against rickettsiae of the typhus and spotted fever groups. Page 6 of 8  Morganella morganii  Biogroup A is ODC + / LDC -  Biogroup E is ODC + / LDC +  Biogroup B is ODC + / LDC +  Biogroup F is ODC - / LDC  Morganella morganii is a Gram-negative, anaerobic rod commonly  Biogroup C is ODC - / LDC - variable found in water, soil, and the intestinal tracts of mammals.  Biogroup D is ODC - / LDC +  Biogroup G is ODC + / LDC -  It was first identified by H. de R. Morgan in 1906 as Morgan’s  Biogroup C was the only one found to be non-susceptible to bacillus. Then in 1946, Morgan’s bacillus was assigned to the tetracycline. established genus Morganella, thus named Morganella morgani.  M. morganii produces extended-spectrum beta-lactamases (ESBL)  Generally, M. morganii has low pathogenicity but there is emerging which contributes to the microbe’s resistance to beta-lactam evidence that M. morganii is an opportunistic pathogen responsible antibiotics. for urinary tract infections (UTI), wound infections, and diarrhea.  M. morganii grows optimally at 22°C.  Most patients, however, recover from the infections with appropriate antibiotic therapy. However, it is resistant to β-lactam  Morganella morganii is found in water, soil, intestinal tracts of antibiotics and can form biofilms. humans, mammals, and reptiles as normal flora.  M. morganii also causes the greatest amount of histamine  The microbe has been isolated from samples of urine, gallbladder, accumulation of any bacteria in food products, such as fish, wine, stool, sputum and other respiratory samples in humans without cheese, and fermented sausage. infection. - When contaminated products are consumed, histamine poisoning, also known as scrombroid poisoning, may occur and even lead to death.  Under usual conditions, M. morganii is typically a benign bacteria in the human body. However, it has been associated with urinary Genome Structure tract infection and postoperative infections.  M. morganii has a complete genome sequence (3,826,919-bp) with  Infections are commonly contracted in a hospital, especially in a G+C content of 51.15% as well as 3,565 protein-coding sequences. immunosuppressed individuals. (A common agent of nosocomial infection)  Genes encoding for drug resistance such as Ampicillin resistance (ampC-ampR), Metallo-β-lactamases (MBL), Tellurite resistance  M. morganaii is also found in post-mortem, non-frozen fish. operon, and Tetracycline resistance were identified in M. When M. morganii is present on food products and post-mortem morganii’s genome. fish, it synthesizes histidine decarboxylase to convert histidine to histamine.  The production of ESBL (Extended Spectrum Beta Lactamase) - The accumulation and consumption of histamine by humans causes a makes the microbe resistant to beta-lactam antibiotics, such as rash, nausea, diarrhea, flushing, sweating, headache, and sometimes penicillins and cephalosporins. ESBL open the beta lactam ring of death. the aforementioned antibiotics and thus inactivates beta-lactam antibiotics.  Freezing the fish at a temperature at or below 0°C completely inhibits histamine production by M. morganii.  The 16S rRNA sequence of the genus Morganella has 1,503 bp and shows 95% similarity to 16S rRNA sequence of some enteric Pathology bacteria, specifically all species in Enterobacter, Klebsiella, Citrobacter, Proteus, Providencia as well as the species Hafnia alvei Morganella morganii has components of a pathogenicity system including adhesion and secretion. Cell Structure and Metabolic Processes - M. morganii adheres to hosts using its type IV pili.  Morganella morganii are Gram-negative, straight rod-shaped bacteria with a diameter of 0.6 0.7 um and a length of 1.0-1.7 um. - It uses a type III secretion system needle complex to inject proteins directly into host cells.  Most M. morganii exhibit motility using peritrichous flagella. - The flagella also enable the bacteria to adhere to surfaces and one another to create biofilms. M. morganaii does have swarming behavior. Treatment  M. morganii does not produce spores.  Current Research findings:  When cultured on an agar plate at 35°C, grayish, opaque colonies of A. Molecular Investigation of extended-spectrum beta-lactamase genes 1 to 2 mm in diameter form and potential drug resistance in clinical isolates of Morganella morganii, Morganella morganii isolates revealed the following findings:  It does not ferment lactose or sucrose; metabolizes levulose and maltose and slowly metabolize galactose, glucose, glycerol. a) M. morganii were considered multidrug resistant because they are resistant to at least three types of antibiotics; piperacillin,  It is a facultative anaerobe, is indole-positive, urease positive and piperacillin-tazobactam, and aztreonam (out of several antibiotics oxidase negative; does not break down cysteine. tested – 19 antibiotics were tested)  M. morganii is divided into two subspecies, M.m. morganii and M.m b) Isolates exposed to these multiple antibiotics have evolved the sibonii - M.m. morganii does not ferment trehalose while the latter ability to produce extended-spectrum beta-lactamase (ESBL). This can. new mutation increased isolates’ resistance to even stronger antibiotics such as ceftriaxone, ceftazidime, and cefotaxime, which  The two subspecies are further divided into biogroups based on were the third- and fourth- generation of cephalosporins three tests: ornithine decarboxylase (ODC), lysine decarboxylase (LDC), and susceptibility to tetracycline. c) A similar study identified M. morganii isolates showing resistance to first-generation antibiotics cephalosporins, ampicillin-  M.m.morganii contains four biogroups (A, B, C, and D) and M.m. clavulinate, gentamicin, piperacillin-tazobactam, and ciprofloxacin. Sibonii contains three biogroups (E, F, and G). All isolates tested harbor the ability to generate ESLB. d) Four genes (CTX-M, SHV, TEM, and OXA) are responsible for ESBL production. Page 7 of 8 B. Characterization of a novel Morganella morganii bacteriophage FSP1 isolated from river water - The bacteriophage FSP1, found in river in Hakodate, Hokkaido, Japan may become the next therapeutic drug for Morganella morganii infections. After 6 hours of incubation at 37 °C only FSP1 formed plaques on M. morganii species, which indicates that this bacteriophage was an exclusive antimicrobial agent for M. morganii. - When the MOI (average number of virus particles infecting a cell) is 1, the total M. morganii cell count decreased from 7.2 to 3.7 log CFU/ml; when MOI is 10, the cell count is zero. However, the M. morganii started to regrow 2 hours to 5 hours after the observation. - In order to prevent phage resistance from happening, one way was to apply phage cocktail to repress the development of resistance. Because of the increasing incidence of M. morganii hospital infections, the threat to our fish food supply, and the antibiotic-resistant nature of M. morganii, a substitute for antibiotics against bacterial growth would be highly useful. Moraganella morgani on BAP Morganella morgani viewed under scanning electron microscope (SEM) Morganella morganii is the only species within the Genus Morganella.  Negative for Lactose, Citrate LDC & H2S.  Urease (+) & Deaminase (+)  An opportunistic pathogen in GIT, UT and wound infections.  Infections are seen in immunocompromised patients and those with prolonged antibiotic therapy.  Septicemia & abscess formation are the more serious infections caused by this organism Page 8 of 8