Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites.

Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins-termed the indolimines-produced by the CRC-associated species Morganella morganii. A non-indolimine-producing M. morganii mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.

Molecular Analysis of blaKPC-2-Harboring Plasmids: Tn4401a Interplasmid Transposition and Tn4401a-Carrying ColRNAI Plasmid Mobilization from Klebsiella pneumoniae to Citrobacter europaeus and Morganella morganii in a Single Patient.

The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales is a public health concern. KPC-encoding blaKPC is predominantly spread by strains of a particular phylogenetic lineage, clonal group 258, but can also be spread by horizontal transfer of blaKPC-carrying plasmids. Here, we report the transfer of a blaKPC-2-harboring plasmid via mobilization from K. pneumoniae to Citrobacter freundii complex and Morganella morganii strains in a single patient. We performed draft whole-genome sequencing to analyze 20 carbapenemase-producing Enterobacterales strains (15 of K. pneumoniae, two of C. freundii complex, and three of M. morganii) and all K. pneumoniae strains using MiSeq and/or MinION isolated from a patient who was hospitalized in New York and Montreal before returning to Japan. All strains harbored blaKPC-2-containing Tn4401a. The 15 K. pneumoniae strains each belonged to sequence type 258 and harbored a Tn4401a-carrying multireplicon-type plasmid, IncN and IncR (IncN+R). Three of these K. pneumoniae strains also possessed a Tn4401a-carrying ColRNAI plasmid, suggesting that Tn4401a underwent interplasmid transposition. Of these three ColRNAI plasmids, two and one were identical to plasmids harbored by two Citrobacter europaeus and three M. morganii strains, respectively. The Tn4401a-carrying ColRNAI plasmids were each 23,753 bp long and incapable of conjugal transfer via their own genes alone, but they mobilized during the conjugal transfer of Tn4401a-carrying IncN+R plasmids in K. pneumoniae. Interplasmid transposition of Tn4401a from an IncN+R plasmid to a ColRNAI plasmid in K. pneumoniae and mobilization of Tn4401a-carrying ColRNAI plasmids contributed to the acquisition of blaKPC-2 in C. europaeus and M. morganii. IMPORTANCE Plasmid transfer plays an important role in the interspecies spread of carbapenemase genes, including the Klebsiella pneumoniae carbapenemase (KPC)-coding gene, blaKPC. We conducted whole-genome sequencing (WGS) analysis and transmission experiments to analyze blaKPC-2-carrying mobile genetic elements (MGEs) between the blaKPC-2-harboring K. pneumoniae, Citrobacter europaeus, and Morganella morganii strains isolated from a single patient. blaKPC-2 was contained within an MGE, Tn4401a. WGS of blaKPC-2-carrying K. pneumoniae, C. europaeus, and M. morganii strains isolated from one patient revealed that Tn4401a-carrying ColRNAI plasmids were generated by plasmid-to-plasmid transfer of Tn4401a from a multireplicon-type IncN and IncR (IncN+R) plasmid in K. pneumoniae strains. Tn4401a-carrying ColRNAI plasmids were incapable of conjugal transfer in C. europaeus and M. morganii but mobilized from K. pneumoniae to a recipient Escherichia coli strain during the conjugal transfer of Tn4401a-carrying IncN+R plasmid. Therefore, Tn4401a-carrying ColRNAI plasmids contributed to the acquisition of blaKPC-2 in C. europaeus and M. morganii.

Wound Infections from Taiwan Cobra (Naja atra) Bites: Determining Bacteriology, Antibiotic Susceptibility, and the Use of Antibiotics-A Cobra BITE Study.

Wound necrosis and secondary infection are common complications after Naja atra bites. Clinical tools to evaluate the infection risk after Taiwan cobra bites are lacking. In this Cobra BITE study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with Taiwan cobra snakebites. Patients with wound infection lacking tissue necrosis were included in developing Cobra BITE score utilizing univariate and multiple logistic regression, as patients with wound necrosis require antibiotics for infection treatment. 8,295,497 emergency department visits occurred in the span of this study, with 195 of those patients being diagnosed as having cobra bites. Of these patients, 23 had wound necrosis, and 30 had wound infection, resulting in a wound infection rate of 27.2% (53/195). Enterococcus faecalis and Morganella morganii were the main bacteria identified in the culture report regardless of whether patients' wounds had necrosis. As per our Cobra BITE score, the three factors predicting secondary wound infection after cobra bites are hospital admission, a white blood cell count (in 103/µL) × by neu-trophil-lymphocyte ratio value of ≥114.23, and the use of antivenin medication. The area under the receiver operating characteristic curve for the Cobra BITE score system was 0.88; ideal sensitivity and specificity were 0.89 and 0.76. This scoring system enables the assessment of wound infections after N. atra bites, and it could be modified and improved in the future for other Naja spp. bites.

Primary intestinal lymphangiectasia diagnosed by video capsule endoscopy in a patient with immunodeficiency presenting with Morganella morganii bacteraemia.

A 24-year-old woman with a medical history of chronic lower extremity oedema, abdominal pain, diarrhoea and recurrent pulmonary infections presented with sepsis from right lower extremity cellulitis. Blood cultures grew Morganella morganii Laboratory evaluation revealed lymphopaenia, hypogammaglobulinaemia, a low CD4+ T-cell count and nutritional deficiencies resulting from protein-losing enteropathy (PLE). CT showed small bowel wall thickening in the jejunum and ileum. Primary intestinal lymphangiectasia (PIL) was the likely diagnosis that explained her PLE and immunodeficiencies. Video capsule endoscopy is an important diagnostic tool for distal small bowel pathology and confirmed patchy areas of lymphangiectasia of the jejunum and ileum. Secondary causes of lymphangiectasia were ruled out. Clinically significant immunodeficiency from PIL has not been frequently documented, and this case adds to the literature of rare infections associated with PIL. Treatment with intravenous antibiotics resolved her septicaemia, while dietary modifications improved her oedema, abdominal pain and diarrhoea.

Whole genome sequencing provides genomic insights into three Morganella morganii strains isolated from bovine rectal swabs in Dhaka, Bangladesh.

Morganella morganii, a gram negative, facultative anaerobic bacterium belonging to the Proteeae tribe of the Morganellaceae family, is an unusual opportunistic pathogen mainly responsible for nosocomial and urinary tract infections. While cattle have long been established as a source of a few zoonotic pathogens, no such data has been recorded for M. morganii despite its ubiquitous presence in nature and a number of animal hosts. In this study, draft genomes were produced of three M. morganii isolates from Bangladeshi cattle. The three isolates, named B2, B3 and B5, possessed an average genome size of 3.9 Mp, a GC% of ∼51% and pan and core genomes of 4637 and 3812 genes, respectively. All strains were bearers of the qnrD1 carrying plasmid Col3M and possessed roughly similar virulence profiles and prophage regions. The strains also carried genes that were unique when compared with other publicly available M. morganii genomes. Many of these genes belonged to metabolic pathways associated with adaptation to environmental stresses and were predicted in silico to be borne in genomic islands. The findings of this study expand on the current understanding of M. morganii''s genomic nature and its adaptation in cattle.

Highly multidrug-resistant Morganella morganii clinical isolates from Nepal co-producing NDM-type metallo-ß-lactamases and the 16S rRNA methylase ArmA.

Morganella morganii can harbour extended-spectrum ß-lactamases and carbapenemases, resulting in increased resistance to multiple antibiotics and a high mortality rate. This study describes the emergence of highly multidrug-resistant clinical isolates of M. morganii from Nepal co-producing NDM-type metallo-ß-lactamases, including NDM-1 and NDM-5, and the 16S rRNA methylase ArmA. This is the first report of M. morganii clinical isolates from Nepal co-producing NDM-1/-5 and ArmA. It is important to establish infection control systems and effective treatments against multidrug-resistant M. morganii.

Genomic analysis of two drug-resistant clinical Morganella morganii strains isolated from UTI patients in Pretoria, South Africa.

Morganella morganii is an opportunistic bacterial pathogen of the Enterobacteriaceae family that is occasionally isolated from clinical (animal and human) specimens with varying resistance profiles. Detailed genomic analyses of drug-resistant M. morganii strains are relatively limited, particularly in Africa, which is also due to their relatively low isolation rates from clinical settings. Here we report on two multidrug-resistant clinical M. morganii isolates from urine specimens of two hospitalized patients in South Africa who presented with urinary tract infections in 2013. The isolates, M006 and E042, were only susceptible to carbapenems, amikacin and tigecycline. One strain, M006, had a novel class 1 integron, ln1484, associated with aadA7, sul1and gcuD gene cassettes and a Col3M plasmid replicase gene. The ln1484 intI1:aadA7:sul1 genes were bracketed by a TnAs3 composite transposon while a tet(B) gene was found on an IS4 family transposon. The rare blaDHA-4 and blaDHA-1 AmpC ß-lactamase genes were identified on the isolates' chromosome. The isolates were phylogenetically distant and closely related to other international strains, suggesting that they were not obtained from a single epidemiological source. Further molecular surveillance is necessary to establish the prevalence of these MDR strains in the tertiary hospital. Moreover antibiotic stewardship and antibiotic sensitivity testing of all clinical isolates should be undertaken after empirical treatment to inform tailored therapy as well as reduce escalation of resistance and associated morbidities and mortalities. SIGNIFICANCE AND IMPACT OF THE STUDY: We report on the first clinical Morganella morganii draft genomes from Africa. The isolates were found in the urine of patients presenting with urinary tract infections (UTIs). Notably, they were resistant to important clinical antibiotics, including those used to treat UTIs. Due to the common occurrence of UTIs, particularly among pregnant women for whom drug options are limited, the presence of antibiotic-resistant uropathogens such as M. morganii is a serious public health concern. We therefore characterized the resistance mechanisms and epidemiology of these isolates to provide further insights into their dissemination and background data for future studies.

Native aortic valve endocarditis with Morganella morganii in a patient with multiple myeloma and valvular amyloidosis: a case report.

BACKGROUND: Patients with multiple myeloma (MM) are known to be immune incompetent and experience higher incidences of infectious diseases. However, infective endocarditis (IE) is rarely observed in patients with MM and Morganella morganii (M. morganii) has rarely been associated with IE. CASE PRESENTATION: A 72-year-old female receiving 4th line treatment for MM presented with fever and concomitant confusion. Urinary culture revealed growth of Escherichia coli, wherefore broadspectrum penicillin and high-dose corticosteroids were initiated. However, blood cultures showed growth of M. morganii. Fluoroquinolone was added due to penicillin-resistance of the Morganella species. Two days after admission, the patient acutely deteriorated with hemodynamic instability. Gentamicin and high dose corticosteroids were added. Echocardiography showed marked aortic valve vegetation with severe aortic valve regurgitation, leading to the diagnosis of bacterial endocarditis of the native aortic valve. Shortly after diagnosis, the patient died. At autopsy, vegetation with gram-negative rods in the native aortic valve was observed, confirming the diagnosis of M. morganii-endocarditis. Additional staining for amyloid confirmed advanced light-chain (AL) amyloidosis with extensive amyloid depositions of the aortic valve and valvular damage as complications of her MM. CONCLUSIONS: Our case suggests that IE with M. morganii was facilitated by the combination of the cardiac amyloidosis with valvular impairment and the profound immune deficiency caused by the several chemo-immunomodulatory treatment lines and the MM itself. This case further illustrates that awareness for rare opportunistic infections in an era with growing potential of combined chemoimmunotherapy is warranted.

Comparative Genome Analysis of Uropathogenic Morganella morganii Strains.

Morganella morganii is an opportunistic bacterial pathogen shown to cause a wide range of clinical and community-acquired infections. This study was aimed at sequencing and comparing the genomes of three M. morganii strains isolated from the urine samples of patients with community-acquired urinary tract infections. Draft genome sequencing was conducted using the Illumina HiSeq platform. The genomes of MM 1, MM 4, and MM 190 strains have a size of 3.82-3.97 Mb and a GC content of 50.9-51%. Protein-coding sequences (CDS) represent 96.1% of the genomes, RNAs are encoded by 2.7% of genes and pseudogenes account for 1.2% of the genomes. The pan-genome containes 4,038 CDS, of which 3,279 represent core genes. Six to ten prophages and 21-33 genomic islands were identified in the genomes of MM 1, MM 4, and MM 190. More than 30 genes encode capsular biosynthesis proteins, an average of 60 genes encode motility and chemotaxis proteins, and about 70 genes are associated with fimbrial biogenesis and adhesion. We determined that all strains contained urease gene cluster ureABCEFGD and had a urease activity. Both MM 4 and MM 190 strains are capable of hemolysis and their activity correlates well with a cytotoxicity level on T-24 bladder carcinoma cells. These activities were associated with expression of RTX toxin gene hlyA, which was introduced into the genomes by a phage similar to Salmonella phage 118970_sal4.

Fístula colecistocutánea / Cholecystocutaneous fistula

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Infection of finger caused by Morganella morganii leading to digital amputation: A case report.

RATIONALE: Digital infection is a common disease in clinic, featured by pain and swelling of digits. As far as we know, no article has reported a case of digital infected by Morganella morganii. PATIENT CONCERNS: A 58-year-old Chinese female complains about whitlow with pain and swelling for 2 weeks. She has a history of diabetes for 10 years. She received incision and drainage before coming to our hospital and preoperative X-ray of left ring finger presented no bone eroded. DIAGNOSIS: She is diagnosed with infection of ring finger caused by M morganii in our hospital. INTERVENTIONS: We perform aggressive operative debridement and drainage firstly. Meanwhile, we provide tissue samples for diagnosis and the result indicates M morganii infection. Then, she is treated with anti-infection therapy and regulation of diabetes. However, 1 week after first surgery, her condition deteriorate presenting bone erosion in distal phalanx of ring finger from X-ray. Considering severity of illness, we decide to perform digital amputation. OUTCOMES: At 3-month follow-up, the patient has a satisfactory result and X-ray shows no bone eroded. LESSONS: Clinicians should consider M morganii, which is rare in hand infection, as a cause of digital infection. This case reminds us that some whitlow is dangerous, amputation should be considered if necessary.

Clinical manifestations, risk factors and prognosis of patients with Morganella morganii sepsis.

BACKGROUND: There are few studies of Morganella bacteremia. We evaluated risk factors and outcome of patients with Morganella bacteremia. METHODS: Medical records of patients with Morganella bacteremia were reviewed (1997-2014). Control group patients with Escherichiacoli sepsis were matched by year of diagnosis and infection acquisition site. RESULTS: The study group included 136 adult patients. Mean age and gender of study and control groups were similar. Complicated soft tissue infection was more prevalent in the study group (30% versus 3.2%, p < 0.05). The Charlson Comorbidity Index (CCI) was higher in the study group (4.3 ± 2.5 versus 3.4 ± 2.8, p < 0.05). Only 78 (62%) of the study patients versus 101 (83%) of the control group (p < 0.05), received appropriate empirical antibiotic treatment. A significantly higher in-hospital mortality rate (42% versus 25%, p < 0.05) as well as longer length of stay (25 ± 22 versus 14 ± 16 days, p < 0.05) was observed in the study group. Multivariate analysis revealed that a debilitative state, a CCI > 4, septic shock and a clinical syndrome other than UTI were all significant risk factors for mortality (p < 0.05). CONCLUSIONS: Patients with Morganellamorganii sepsis had more co-morbidities and a worse degree of sepsis. There is an increased risk of inappropriate empirical treatment, longer hospitalization and higher death rate.

Development and evaluation of an improved quantitative loop-mediated isothermal amplification method for rapid detection of Morganella morganii.

A point-of-care diagnostic kit was developed for detection of Morganella morganii using optimized loop-mediated isothermal amplification (LAMP) technique within less than an hour. In that regard, dimethyl sulfoxide (DMSO) was utilized together with betaine and all variables were optimized to improve the efficiency of the method. Moreover, surface presentation of antigens protein was targeted and six unique primers were designed. Endpoint turbidity analysis was performed at 550 nm to measure the tetravalent anion (pyrophosphate) released during the reaction. The specificity of the method was evaluated using nine closely related bacterial species as well as its sensitivity. It was shown that the improved LAMP assay could significantly distinguish M. morganii from other bacteria while the sensitivity was determined to be 0.2 CFU mL-1.

A novel cfr-carrying Tn7 transposon derivative characterized in Morganella morganii of swine origin in China.

OBJECTIVES: To characterize the presence and genetic environment of the multiresistance gene cfr in bacterial isolates from a swine farm. METHODS: A total of 97 bacterial isolates, recovered from 32 faecal swabs obtained on one farm, were tested for the presence of the cfr gene by PCR. Species identification of the one cfr-positive strain was conducted using the BD PhoenixTM 100 Automated Microbiology System. Susceptibility testing was carried out by broth microdilution. The genetic environment of the cfr gene was analysed by WGS. RESULTS: The Morganella morganii isolate BCMM24 was the only cfr-positive strain. The cfr gene, as well as 15 other resistance genes, is located on a novel 111238 bp transposon derived from Tn7, designated as Tn6451, which comprises various genetic materials including a novel class 1 integron with five gene cassettes. The cfr-containing region consists of a novel genetic structure IS26-cfr-ΔTn554 tnpB-ΔTn3 family tnpA-IS26, differing from previous reports. Two-step PCR results show that the structure can be looped out and that Tn6451 cannot be excised from the chromosome. CONCLUSIONS: To the best of our knowledge, we report the cfr gene in M. morganii for the first time. The cfr gene and 15 other resistance genes are located on a novel Tn7 transposon derivative, suggesting that the Tn7 transposon may act as a reservoir for various antimicrobial resistance genes and more Tn7 derivatives carrying multiple resistance genes are likely to be discovered in Gram-negative bacteria of both animal and human origin.

[Encrusted Pyelitis during a case of Thrombotic Thrombocytopenic Purpura].

Encrusted pyelitis is a chronic urinary tract infection associated with mucosal encrustation induced by urea splitting bacteria. More than 40 bacteria have been implicated but the most frequent is Corynebacterium group D2. Predisposing factors are debilitating chronic diseases and preexisting urological procedures. Immunosoppression is an important cofactor. For these reasons the disease is almost always nosocomially acquired and renal transplant recipients are at particular risk. The symptoms are not specific and long lasting: dysuria, flank pain and gross haematuria are the most frequent; fever is present in two-thirds. The demonstration of urine splitting bacteria in constantly alkaline urines and radiological evidence of extensive calcification of pelvicalyceal system, ureter and bladder at US or CT scan in a clinical context of predisposing factors are the mainstay of diagnosis. Treatment is based on adapted antibiotic therapy, acidification of urine and excision of plaques of calcified encrustation. The prognosis relies on timing of diagnosis; delay can be detrimental and result in patient's death and graft loss. We describe a unique case of 69-year-old man with two contemporary diseases: autoimmune thrombotic thrombocytopenic purpura and encrusted pyelitis with a fatal evolution.