Doenças causadas por enterobacteriaceae morganella morganii e a resistência aos fármacos beta lactâmicos. / Diseases caused by enterobacteriaceae morganella morganii and resistance to beta lactamic drugs.

Introdução: Morganella morganii uma bactéria gram-negativa, que se encontra normalmente na flora intestinal normal tanto de humanos quanto em mamíferos. Faz parte da maior família de bactérias gram-negativas de importância clínica as Enterobacteriaceae, ela e conhecida por causar diversas patologias em humanos. Objetivos: A bactéria em discursão tem muita importância clinica pelo fato de causar diversas patologias. Este estudo pretende explorar a resistência aos fármacos beta-lactâmicos, e as diversas doenças que a Morganella morganii causam nos seres humanos. Metodologia: É um estudo básico, que tem como objetivo um estudo exploratório, que tem como finalidade unir informações sobre o tema abordado. Quanto à abordagem trata-se de uma pesquisa qualitativa, no que se refere aos procedimentos técnicos é uma pesquisa bibliográfica que tem como base a pesquisa de materiais já publicados. Conclusão: Com o aumento do número de relatos de doenças a cerca da Morganella morganii e preciso desenvolver um método rápido de detecção e mais estudos a respeito dessa bactéria, pois ela esta se tornando cada vez mais resistente aos antibióticos. Este patógeno deveria ser clinicamente significativo, e os médicos deveriam colocar essa bactéria na lista de possíveis causas das infecções, na hora do atendimento medico ao paciente. Sugerem-se mais estudos a respeito desse microrganismo para ser possivelmente classificada como um patógeno Negligenciado.

Development of a Molecular Serotyping Scheme for Morganella morganii

Morganella morganii, which is often regarded as a human commensal organism, can be an opportunistic pathogen, causing a variety of clinical infections with serious morbidity and mortality. An efficient and convenient method for subtyping and identifying M. morganii strains in epidemiological surveillance and control is urgently needed. Serotyping based on bacterial surface polysaccharide antigens (O-antigen or K-antigens) is a standard subtyping method for many gram-negative bacteria. Here, through whole genome sequencing and comparative genomics analysis of 27 strains, we developed a molecular serotyping scheme based on the genetic variation of O-antigen gene clusters (O-AGC) in M. morganii, and 11 distinct O-AGC types were identified. A conventional serotyping scheme was also developed by the production of antisera and agglutination experiments, which was shown to be perfectly consistent with the molecular serotyping scheme, confirming that the variation in M. morganii O-AGC correlated with phenotypic O-antigen diversification. Furthermore, a microsphere-based suspension array (MSA) with high specificity was developed based on the specific genes within each O-AGC type. The sensitivity of MSA was determined to be 0.1 ng of genomic DNA and 103 CFU of pure culture. We further analyzed 104 M. morganii genomes available in GenBank, and an additional six novel O-AGC types were identified, indicating that the extension of this molecular serotyping scheme is convenient. Our work provides an important tool for the detection and epidemiological surveillance of M. morganii, and this method has the potential to be widely utilized, especially for bacterial genera/species without an efficient typing approach.

Genetic and Phenotypic Diversity of Morganella morganii Isolated From Cheese

The bacterium Morganella morganii can produce the biogenic amines (BA) cadaverine, putrescine, and histamine in vitro and is responsible for high histamine concentrations in fish products. These BA can have toxic effects upon ingestion and are undesired in food. The purpose of this study was to characterize the phenotype and genotype of 11 M. morganii isolated from cheese in regard to the BA formation. In addition, we investigated the phylogeny, trehalose fermentation ability, and antibiotic resistance of the cheese isolates. To do so, we sequenced their genomes using both long and short read technologies. Due to the presence of the trehalose operon and the ability to ferment trehalose, the cheese isolates can be assigned to the subsp. sibonii. Comparative genomics with public available M. morganii genomes shows that the genomes of the cheese isolates cluster together with other subsp. sibonii genomes. All genomes between subsp. morganii and subsp. sibonii are separated by an average nucleotide identity (ANI) of less than 95.0%. Therefore, the subspecies could represent two distinct species. Nine of the strains decarboxylated lysine yielding cadaverine in vitro. This metabolic activity is linked to a previously unknown gene cluster comprising genes encoding a lysine-tRNA ligase (lysS), an HTH-transcriptional regulator (argP), a cadaverine-lysine antiporter (cadB), and a lysine decarboxylase (cadA). The formation of putrescine is linked to the speF gene encoding an ornithine decarboxylase. The gene is disrupted in five strains by an insertion sequence, and these strains only exhibit a weak putrescine production. Antimicrobial susceptibility profiling revealed that all cheese strains are resistant to tetracycline, chloramphenicol, tigecycline, colistin, and ampicillin. These phenotypes, except for colistin which is intrinsic, could be linked to antimicrobial resistance genes located on the chromosome.

Molecular Analysis of bla KPC-2 -Harboring Plasmids: Tn 4401a Interplasmid Transposition and Tn 4401a -Carrying ColRNAI Plasmid Mobilization from Klebsiella pneumoniae to Citrobacter europaeus and Morganella morganii in a Single Patient

Plasmid transfer plays an important role in the interspecies spread of carbapenemase genes, including the Klebsiella pneumoniae carbapenemase (KPC)-coding gene, bla KPC . We conducted whole-genome sequencing (WGS) analysis and transmission experiments to analyze bla KPC-2 -carrying mobile genetic elements (MGEs) between the bla KPC-2 -harboring K. pneumoniae , Citrobacter europaeus , and Morganella morganii strains isolated from a single patient. bla KPC-2 was contained within an MGE, Tn 4401a .

175. Antibiotic Resistance in Select Gram-negative Bacteria Over the Past Decade Among Hospitalized Veterans Nationally

Background Public health institutions including the World Health Organization and the United States Centers for Disease Control and Prevention (CDC) have recognized the threat of antibiotic resistant infections caused by Gram-negative bacteria. These bacteria are particularly concerning as they can demonstrate resistance to all available antibiotic classes through various mechanisms. We set out to assess antibiotic resistance trends in Gram-negative bacteria to optimize antimicrobial stewardship and infection control initiatives in our health system. Methods We identified positive cultures (1st per patient per month) of P. aeruginosa and select Enterobacterales (Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, Serratia marcescens) collected from patients hospitalized at Veterans Affairs (VA) Medical Centers nationally from 2011 to 2020. Time trends were assessed with joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals (CIs) for the following resistance phenotypes utilizing CDC definitions: multi-drug resistance (MDR), extended-spectrum beta-lactamase (ESBL), and carbapenem (CR) and fluoroquinolone (FR) resistance. Results We included 496,384 isolates in our study: E. coli (32.6%), Klebsiella (20%), P. aeruginosa (18.9%), P. mirabilis (11.5%), Enterobacter (7.8%), Citrobacter (3.7%), S. marcescens (2.9%), and M. morganii (2.6%). Trends in resistance are shown in the figures. MDR, ESBL, CR, and FR decreased significantly (p< 0.05) over the study period for most of the organisms assessed, with the exception of MDR and ESBL E. coli and CR P. mirabilis which remained stable, and CR M. morganii which increased significantly by 7.1% per year (95% CI 0.2% to 14.5%). The largest decreases were in CR E. coli by 29.5% per year (95% CI -36.5% to -21.8%), CR Klebsiella by 23.7% per year (95% CI -27.6% to -19.5%), and MDR and CR S. marcescens by 12.2% (95% CI -14.4% to -9.9%) and 12.3% per year (95% CI -16.2% to -8.1%), respectively. Figure 1. Antibiotic resistance trends in Citrobacter spp., E. coli, Enterobacter spp., and Klebsiella spp. Antibiotic resistance trends (by percentage) in (a) Citrobacter spp, (b) E. coli, (c) Enterobacter spp, and (d) Klebsiella spp from 2011-2020. Abbreviations: MDR = multi-drug resistance (defined as non-susceptible to at least 1 drug in at least 3 of the following categories: extended-spectrum cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin/tazobactam); ESBL = extended spectrum beta-lactamase (defined as non-susceptible to at least 1 of the following drugs: cefepime, ceftriaxone, cefotaxime, ceftolozane/tazobactam, ceftazidime/avibactam); CR = carbapenem resistance (defined as non-susceptible to at least 1 carbapenem); FR = fluoroquinolone resistance (defined as non-susceptible to at least 1 fluoroquinolone); AAPC = annual average percentage change; CI = confidence interval. Figure 2. Antibiotic resistance trends in Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, and Morganella morganii. Antibiotic resistance trends (by percentage) in (e) Pseudomonas aeruginosa, (f) Proteus mirabilis, (g) Serratia marcescens, and (h) Morganella morganii from 2011-2020. Abbreviations: MDR = multi-drug resistance (defined as non-susceptible to at least 1 drug in at least 3 of the following categories: extended-spectrum cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin/tazobactam); ESBL = extended spectrum beta-lactamase (defined as non-susceptible to at least 1 of the following drugs: cefepime, ceftriaxone, cefotaxime, ceftolozane/tazobactam, ceftazidime/avibactam); CR = carbapenem resistance (defined as non-susceptible to at least 1 carbapenem); FR = fluoroquinolone resistance (defined as non-susceptible to at least 1 fluoroquinolone); AAPC = annual average percentage change; CI = confidence interval. Conclusion Overall, MDR, ESBL, CR, and FR in Enterobacterales and P. aeruginosa decreased from 2011 to 2020 in the VA. These results may be related to the robust infection control and antimicrobial stewardship programs instituted among VA Medical Centers nationally. Disclosures Kerry LaPlante, PharmD, Merck (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc (Research Grant or Support) Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)

Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii

Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.

Antimicrobial Resistance Patterns in Diabetic Foot Infections, an Epidemiological Study in Northeastern Italy

This study is a retrospective epidemiological assessment of bacterial species isolated from a cohort of out-patients with diabetic foot infections referred to our “Diabetic Foot Unit” over one year, with particular attention to index pathogens, as identified by the EARS Network. Staphylococcus aureus and Pseudomonas aeruginosa accounted for 33.5% and 11.9% of cases, respectively. MRSA was isolated in 27.1% of patients, with 14.06% showing additional resistance to three antimicrobial classes. Pseudomonas aeruginosa presented extensive resistance to fluoroquinolones (57.3%), which was associated with resistance to piperacillin in 17.6% or to carbapenems in 23.5% of cases. Other pathogens, such as methicillin resistant Staphylococcus epidermidis, Escherichia coli and Morganella morganii ESBL and Enterococcus faecium VRE, were also found.