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Single-Molecule Sequencing (PacBio) of the Staphylococcus capitis NRCS-A Clone Reveals the Basis of Multidrug Resistance and Adaptation to the Neonatal Intensive Care Unit Environment.

ABSTRACT: The multi-resistant Staphylococcus capitis clone NRCS-A has recently been described as a major pathogen causing nosocomial, late-onset sepsis (LOS) in preterm neonates worldwide. NRCS-A representatives exhibit an atypical antibiotic resistance profile. Here, the complete closed genome (chromosomal and plasmid sequences) of NRCS-A prototype strain CR01 and the draft genomes of three other clinical NRCS-A strains from Australia, Belgium and the United Kingdom are annotated and compared to available non-NRCS-A S. capitis genomes. Our goal was to delineate the uniqueness of the NRCS-A clone with respect to antibiotic resistance, virulence factors and mobile genetic elements. We identified 6 antimicrobial resistance genes, all carried by mobile genetic elements. Previously described virulence genes present in the NRCS-A genomes are shared with the six non-NRCS-A S. capitis genomes. Overall, 63 genes are specific to the NRCS-A lineage, including 28 genes located in the methicillin-resistance cassette SCCmec. Among the 35 remaining genes, 25 are of unknown function, and 9 correspond to an additional type I restriction modification system (n = 3), a cytosine methylation operon (n = 2), and a cluster of genes related to the biosynthesis of teichoic acids (n = 4). Interestingly, a tenth gene corresponds to a resistance determinant for nisin (nsr gene), a bacteriocin secreted by potential NRCS-A strain niche competitors in the gut microbiota. The genomic characteristics presented here emphasize the contribution of mobile genetic elements to the emergence of multidrug resistance in the S. capitis NRCS-A clone. No NRCS-A-specific known virulence determinant was detected, which does not support a role for virulence as a driving force of NRCS-A emergence in NICUs worldwide. However, the presence of a nisin resistance determinant on the NRCS-A chromosome, but not in other S. capitis strains and most coagulase-negative representatives, might confer a competitive advantage to NRCS-A strains during the early steps of gut colonization in neonates. This suggests that the striking adaptation of NRCS-A to the NICU environment might be related to its specific antimicrobial resistance and also to a possible enhanced ability to challenge competing bacteria in its ecological niche.

SUBMITTER: Simoes PM

PROVIDER: S-EPMC5157051 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Single-Molecule Sequencing (PacBio) of the <i>Staphylococcus capitis</i> NRCS-A Clone Reveals the Basis of Multidrug Resistance and Adaptation to the Neonatal Intensive Care Unit Environment.

Simões Patrícia Martins PM Lemriss Hajar H Dumont Yann Y Lemriss Sanâa S Rasigade Jean-Philippe JP Assant-Trouillet Sophie S Ibrahimi Azeddine A El Kabbaj Saâd S Butin Marine M Laurent Frédéric F

Frontiers in microbiology 20161215

The multi-resistant <i>Staphylococcus capitis</i> clone NRCS-A has recently been described as a major pathogen causing nosocomial, late-onset sepsis (LOS) in preterm neonates worldwide. NRCS-A representatives exhibit an atypical antibiotic resistance profile. Here, the complete closed genome (chromosomal and plasmid sequences) of NRCS-A prototype strain CR01 and the draft genomes of three other clinical NRCS-A strains from Australia, Belgium and the United Kingdom are annotated and compared to a ...[more]

PMID: 28018320

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Project description:The clone Staphylococcus capitis NRCS-A is responsible for late-onset sepsis in neonatal intensive care units (NICUs) worldwide. Over time, this clone has evolved into three subgroups that are increasingly adapted to the NICU environment. This study aimed to decipher the mechanisms involved in NRCS-A persistence in NICUs. Twenty-six S. capitis strains belonging to each of the three NRCS-A clone subgroups and two other non-NRCS-A groups from neonates (alpha clone) or from adult patients ("other strains") were compared based on growth kinetics and ability to form biofilm as well as tolerance to desiccation and to different disinfectants. S. capitis biofilm formation was enhanced in rich medium and decreased under conditions of nutrient stress for all strains. However, under conditions of nutrient stress, NRCS-A strains presented an enhanced ability to adhere and form a thin biofilm containing more viable and culturable bacteria (mean 5.7 log10 CFU) than the strains from alpha clone (mean, 1.1 log10 CFU) and the "other strains" (mean, 4.2 log10 CFU) (P < 0.0001). The biofilm is composed of bacterial aggregates with a matrix mainly composed of polysaccharides. The NRCS-A clone also showed better persistence after a 48-h desiccation. However, disinfectant tolerance was not enhanced in the NRCS-A clone in comparison with that of strains from adult patients. In conclusion, the ability to form biofilm under nutrient stress and to survive desiccation are two major advantages for clone NRCS-A that could explain its ability to persist and settle in the specific environment of NICU settings. IMPORTANCE Neonatal intensive care units (NICUs) host extremely fragile newborns, including preterm neonates. These patients are very susceptible to nosocomial infections, with coagulase-negative staphylococci being the species most frequently involved. In particular, a Staphylococcus capitis clone named NRCS-A has emerged worldwide specifically in NICUs and is responsible for severe nosocomial sepsis in preterm neonates. This clone is specifically adapted to the NICU environment and is able to colonize and maintain on NICU surfaces. The present work explored the mechanisms involved in the persistence of the NRCS-A clone in the NICU environment despite strict hygiene measures. The ability to produce biofilm under nutritional stress and to resist desiccation appear to be the two main advantages of NRCS-A in comparison with other strains. These findings are pivotal to provide clues for subsequent development of targeted methods to combat NRCS-A and to stop its dissemination.

Project description:This study was conducted in order to know the colonization rate of MDR enterobacteria in neonates during their hospitalization in neonatal intensive care unit (NICU). Furthermore, we investigated risk factors for potential colonization and molecular epidemiology of isolated resistant bacteria. This prospective study was carried out in the neonatology and intensive care unit department of the University Hospital of Fez (Morocco) from February 2013 to July 2015. All consecutive admitted newborns were screened for intestinal and nasal carriage of MDR enterobacteria at admission of the babies and during the hospitalization. During the study period, a total of 641 Enterobacteriaceae were isolated and Klebsiella pneumoniae was the predominated bacteria. Bacterial identification and antibiograms were performed according to the international standards. On admission, 455 newborns were screened. A median age of these newborns was 1 day with an extended 147 days and their average weight was 2612 ± 1023 grams. 22.4% of neonates were found colonized by an ESBL producing Enterobacteriaceae (ESBL-E), 8.7% by a carbapenemases producing Enterobacteriaceae (CPE). During hospitalization, 207 of newborns were included in the acquisition study. 59.4% of newborns acquired an ESBL-E during their stay, 12.5% has acquired CPE. The blaCTXM-15 gene was the most frequently detected (81.2%) among ESBL-E. While, all CPE has expressed the blaOXA-48 gene exclusively. Two risk factors have been significantly associated with MDR enterobacteria colonization at admission which are newborns admission from maternity of the university hospital (95% CI, 1.859-5.129, P = 0.000) and neurological distress (95% CI, 1.038 to 4.694, P = 0.040). During hospitalization, the none risk factor was significantly associated with the carriage of MDR-E. The high rate of colonization, the MDR enterobacteria and the resistance genes found represent good indicator of cross-transmission in the NICU. An active strategy to control the spread of MDR enterobacteria should be applied.

Dataset Information

Single-Molecule Sequencing (PacBio) of the Staphylococcus capitis NRCS-A Clone Reveals the Basis of Multidrug Resistance and Adaptation to the Neonatal Intensive Care Unit Environment.

Publications

Single-Molecule Sequencing (PacBio) of the <i>Staphylococcus capitis</i> NRCS-A Clone Reveals the Basis of Multidrug Resistance and Adaptation to the Neonatal Intensive Care Unit Environment.

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