Characterization of a Clinical Enterobacter hormaechei Strain Belonging to Epidemic Clone ST418 Co-carrying blaNDM-1, blaIMP-4 and mcr-9.1

An Enterobacter hormaechei isolate (ECL-90) simultaneously harboring blaNDM-1, blaIMP-4 and mcr-9.1 was recovered from the secretion specimen of a 24-year-old male patient in a tertiary hospital in China. The whole genome sequencing of this isolate was complete, and 4 circular plasmids with variable sizes were detected. Multi-locus sequence typing (MLST) analysis assigned the isolate to ST418, known as a carbapenemase-producing epidemic clone in China. blaIMP-4 and mcr-9.1 genes were co-carried on an IncHI2/2A plasmid (pECL-90-2) and blaNDM-1 was harbored by an IncX3 plasmid (pECL-90-3). The genetic context of mcr-9.1 was identified as a prevalent structure, “rcnR-rcnA-pcoE-pcoS-IS903-mcr-9-wbuC”, which is a relatively unitary model involved in the mobilization of mcr-9. Meanwhile, blaNDM-1 gene was detected within a globally widespread structure known as NDM-GE-U.S (“ISAba125–blaNDM-1–blaMBL”). Our study warrants that the convergence of genes mediating resistance to last-resort antibiotics in epidemic clones would largely facilitate their widespread in clinical settings, thus representing a potential challenge to clinical treatment and public health.

Population Analysis of Staphylococcus aureus Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia

ABSTRACT Staphylococcal superantigens (SAgs) are a family of secreted toxins that stimulate T cell activation and are associated with an array of diseases in humans and livestock. Most SAgs produced by Staphylococcus aureus are encoded by mobile genetic elements, such as pathogenicity islands, bacteriophages, and plasmids, in a strain-dependent manner. Here, we carried out a population genomic analysis of >800 staphylococcal isolates representing the breadth of S. aureus diversity to investigate the distribution of all 26 identified SAg genes. Up to 14 SAg genes were identified per isolate with the most common gene selw (encoding a putative SAg, SElW) identified in 97% of isolates. Most isolates (62.5%) have a full-length open reading frame of selw with an alternative TTG start codon that may have precluded functional characterization of SElW to date. Here, we demonstrate that S. aureus uses the TTG start codon to translate a potent SAg SElW that induces Vβ-specific T cell proliferation, a defining feature of classical SAgs. SElW is the only SAg predicted to be expressed by isolates of the CC398 lineage, an important human and livestock epidemic clone. Deletion of selw in a representative CC398 clinical isolate, S. aureus NM001, resulted in complete loss of T cell mitogenicity in vitro, and in vivo expression of SElW by S. aureus increased the bacterial load in the liver during bloodstream infection of SAg-sensitive HLA-DR4 transgenic mice. Overall, we report the characterization of a novel, highly prevalent, and potent SAg that contributes to the pathogenesis of S. aureus infection. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen associated with an array of diseases, including life-threatening necrotizing pneumonia and infective endocarditis. The success of S. aureus as a pathogen has been linked in part to its ability to manipulate the host immune response through the secretion of toxins and immune evasion molecules. The staphylococcal superantigens (SAgs) have been studied for decades, but their role in S. aureus pathogenesis is not well understood, and an appreciation for how SAgs manipulate the host immune response to promote infection may be crucial for the development of novel intervention strategies. Here, we characterized a widely prevalent, previously cryptic, staphylococcal SAg, SElW, that contributes to the severity of S. aureus infections caused by an important epidemic clone of S. aureus CC398. Our findings add to the understanding of staphylococcal SAg diversity and function and provide new insights into the capacity of S. aureus to cause disease.

Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae

In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics.

Characterization of a clinical Enterobacter hormaechei strain belonging to epidemic clone ST418 co-carrying blaNDM-1, blaIMP-4 and mcr-9.1

An Enterobacter hormaechei isolate (ECL-90) simultaneously harboring blaNDM-1, blaIMP-4 and mcr-9.1 was recovered from the secretion specimen of a 24-year-old male patient in a tertiary hospital in China. The whole genome sequencing of this isolate was complete, and 4 circular plasmids with variable sizes were detected. MLST analysis assigned the isolate to ST418, known as a carbapenemase-producing epidemic clone in China. blaIMP-4 and mcr-9.1 genes were co-carried on an IncHI2/2A plasmid (pECL-90-2) and blaNDM-1 was harbored by an IncX3 plasmid (pECL-90-3). The genetic context of mcr-9.1 was identified as a prevalent structure, “rcnR-rcnA-pcoE-pcoS-IS903-mcr-9-wbuC”, which is a relatively unitary model involved in the mobilization of mcr-9. Meanwhile, blaNDM-1 gene was detected within a globally widespread structure known as NDM-GE-U.S (“ISAba125– blaNDM-1–blaMBL”). Our study warrants that the convergence of genes mediating resistance to last-resort antibiotics in epidemic clones would largely facilitate their widespread in clinical settings, thus representing a potential challenge to clinical treatment and public health.ImportanceCarbapenemase-producing Enterobacteriaceae (CPE) spread at a high rate and colistin is the last-resort therapeutic for the infection caused by CPE. However, the emergence of plasmid-borne mcr genes highly facilitates the wide dissemination of colistin resistance, thus largely threatens the clinical use of colistin. Here, we for the first time characterized a clinical Enterobacter hormaechei strain co-producing blaNDM-1, blaIMP-4 and mcr-9.1 belonging to an epidemic clone (ST418). The accumulation of genes mediating resistance to last-resort antibiotics in epidemic clones would largely facilitate their widespread in clinical settings, which may cause disastrous consequence with respect to antimicrobial resistance. Understanding how resistance genes were accumulated in a single strain could help us to track the evolutionary trajectory of drug resistance. Our finding highlights the importance of surveillance on the epidemic potential of colistin-resistant CPE, and effective infection control measures to prevent the resistance dissemination.

Risk factors for Clostridioides difficile infection and colonization among patients admitted to an intensive care unit in Shanghai, China

Background Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. Methods Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. Results Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR = 13.993), metabolic disorder (OR = 7.972), and treatment with fluoroquinolone (OR = 42.696) or combined antibiotics (OR = 2.856). CDC patients were characterized by prolonged hospital stay (OR = 1.137), increased number of comorbidities (OR = 36.509), respiratory diseases (OR = 0.043), and treatment with vancomycin (OR = 18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR = 0.042; CDC: OR = 0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A + B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A + B+ and the epidemic clone was ST81. Conclusions The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile. Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.

Risk factors for Clostridioides difficile infection and colonization among patients admitted to an intensive care unit in Shanghai, China

Background: Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. Methods: Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. Results: Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR=13.993), metabolic disorder (OR=7.972), and treatment with fluoroquinolone (OR=42.696) or combined antibiotics (OR=2.856). CDC patients were characterized by prolonged hospital stay (OR=1.137), increased number of comorbidities (OR=36.509), respiratory diseases (OR=0.043), and treatment with vancomycin (OR=18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR=0.042; CDC: OR=0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A+B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A+B+ and the epidemic clone was ST81. Conclusions: The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile . Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.

Risk factors for Clostridioides difficile infection and colonization among patients admitted to an intensive care unit in Shanghai, China

Background: Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. Methods: Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. Results: Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR=13.993), metabolic disorder (OR=7.972), and treatment with fluoroquinolone (OR=42.696) or combined antibiotics (OR=2.856). CDC patients were characterized by prolonged hospital stay (OR=1.137), increased number of comorbidities (OR=36.509), respiratory diseases (OR=0.043), and treatment with vancomycin (OR=18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR=0.042; CDC: OR=0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A+B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A+B+ and the epidemic clone was ST81. Conclusions: The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile . Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.