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Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of immunocompromised patients.

ABSTRACT: OBJECTIVES:Corynebacterium striatum is an emerging multidrug-resistant (MDR) pathogen of immunocompromised and chronically ill patients. The objective of these studies was to provide a detailed genomic analysis of disease-causing C. striatum and determine the genomic drivers of resistance and resistance-gene transmission. METHODS:A multi-institutional and prospective pathogen genomics programme flagged seven MDR C. striatum infections occurring close in time, and specifically in immunocompromised patients with underlying respiratory diseases. Whole genome sequencing was used to identify clonal relationships among strains, genetic causes of antimicrobial resistance, and their mobilization capacity. Matrix-assisted linear desorption/ionization-time-of-flight analyses of sequenced isolates provided curated content to improve rapid clinical identification in subsequent cases. RESULTS:Epidemiological and genomic analyses identified a related cluster of three out of seven C. striatum among lung transplant patients who had common procedures and exposures at an outlying institution. Genomic analyses further elucidated drivers of the MDR phenotypes, including resistance genes mobilized by IS3504 and ISCg9a-like insertion sequences. Seven mobilizable resistance genes were localized to a common chromosomal region bounded by unpaired insertion sequences, suggesting that a single recombination event could spread resistance to aminoglycosides, macrolides, lincosamides and tetracyclines to naive strains. CONCLUSION:In-depth genomic studies of MDR C. striatum reveal its capacity for clonal spread within and across healthcare institutions and identify novel vectors that can mobilize multiple forms of drug resistance, further complicating efforts to treat infections in immunocompromised populations.

SUBMITTER: Nudel K

PROVIDER: S-EPMC6037610 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of immunocompromised patients.

Nudel K K Zhao X X Basu S S Dong X X Hoffmann M M Feldgarden M M Allard M M Klompas M M Bry L L

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 20180109 9

<h4>Objectives</h4>Corynebacterium striatum is an emerging multidrug-resistant (MDR) pathogen of immunocompromised and chronically ill patients. The objective of these studies was to provide a detailed genomic analysis of disease-causing C. striatum and determine the genomic drivers of resistance and resistance-gene transmission.<h4>Methods</h4>A multi-institutional and prospective pathogen genomics programme flagged seven MDR C. striatum infections occurring close in time, and specifically in i ...[more]

PMID: 29326010

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Project description:Corynebacterium striatum is a Gram-positive bacterium that is straight or slightly curved and non-spore-forming. Although it was originally believed to be a part of the normal microbiome of human skin, a growing number of studies have identified it as a cause of various chronic diseases, bacteremia, and respiratory infections. However, despite its increasing importance as a pathogen, the genetic characteristics of the pathogen population, such as genomic characteristics and differences, the types of resistance genes and virulence factors carried by the pathogen and their distribution in the population are poorly understood. To address these knowledge gaps, we conducted a pan-genomic analysis of 314 strains of C. striatum isolated from various tissues and geographic locations. Our analysis revealed that C. striatum has an open pan-genome, comprising 5692 gene families, including 1845 core gene families, 2362 accessory gene families, and 1485 unique gene families. We also found that C. striatum exhibits a high degree of diversity across different sources, but strains isolated from skin tissue are more conserved. Furthermore, we identified 53 drug resistance genes and 42 virulence factors by comparing the strains to the drug resistance gene database (CARD) and the pathogen virulence factor database (VFDB), respectively. We found that these genes and factors are widely distributed among C. striatum, with 77.7% of strains carrying 2 or more resistance genes and displaying primary resistance to aminoglycosides, tetracyclines, lincomycin, macrolides, and streptomycin. The virulence factors are primarily associated with pathogen survival within the host, iron uptake, pili, and early biofilm formation. In summary, our study provides insights into the population diversity, resistance genes, and virulence factors ofC. striatum from different sources. Our findings could inform future research and clinical practices in the diagnosis, prevention, and treatment of C. striatum-associated diseases.

Project description:The Gram-negative bacterium Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments. However, little is known about this species or its antibiotic resistance mechanisms. We used biochemical tests, antibiotic susceptibility experiments, and whole-genome sequencing to characterize an environmental C. gilardii isolate. Like clinical isolates, this isolate was resistant to meropenem, gentamicin, and other antibiotics. Resistance to these antibiotics appeared to be related to the large number of intrinsic antibiotic resistance genes found in this isolate. As determined by comparative genomics, this resistome was also well conserved in the only two other C. gilardii strains sequenced to date. The intrinsic resistome of C. gilardii did not include the colistin resistance gene mcr-5, which was in a transposon present only in one strain. The intrinsic resistome of C. gilardii was comprised of (i) many multidrug efflux pumps, such as a homolog of the Pseudomonas aeruginosa MexAB-OprM pump that may be involved in resistance to meropenem, other β-lactams, and aminoglycosides; (ii) a novel β-lactamase (OXA-837) that decreases susceptibility to ampicillin but not to other β-lactams tested; (iii) a new aminoglycoside 3-N-acetyltransferase [AAC(3)-IVb, AacC10] that decreases susceptibility to gentamicin and tobramycin; and (iv) a novel partially conserved aminoglycoside 3"-adenylyltransferase [ANT(3")-Ib, AadA32] that decreases susceptibility to spectinomycin and streptomycin. These findings provide the first mechanistic insight into the intrinsic resistance of C. gilardii to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy.IMPORTANCE Cupriavidus gilardii is a bacterium that is gaining increasing attention both as an infectious agent and because of its potential use in the detoxification of toxic compounds and other biotechnological applications. In recent years, however, there has been an increasing number of reported infections, some of them fatal, caused by C. gilardii These infections are hard to treat because this bacterium is naturally resistant to many antibiotics, including last-resort antibiotics, such as carbapenems. Moreover, this bacterium often becomes resistant to additional antibiotics during therapy. However, little is known about C. gilardii and its antibiotic resistance mechanisms. The significance of our research is in providing, for the first time, whole-genome information about the natural antibiotic resistance genes found in this bacterium and their conservation among different C. gilardii strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen.

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Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of immunocompromised patients.

Publications

Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of immunocompromised patients.

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