{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ruiz C"],"funding":["HHS | National Institutes of Health","NIGMS NIH HHS"],"pagination":["e00631-19"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6796972"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(5)"],"pubmed_abstract":["The Gram-negative bacterium <i>Cupriavidus gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> strains sequenced to date. The intrinsic resistome of <i>C. gilardii</i> did not include the colistin resistance gene <i>mcr-5</i>, which was in a transposon present only in one strain. The intrinsic resistome of <i>C. gilardii</i> was comprised of (i) many multidrug efflux pumps, such as a homolog of the <i>Pseudomonas aeruginosa</i> 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-<i>N</i>-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 <i>C. gilardii</i> to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy.<b>IMPORTANCE</b><i>Cupriavidus gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen."],"journal":["mSphere"],"pubmed_title":["Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen Cupriavidus gilardii."],"pmcid":["PMC6796972"],"funding_grant_id":["RL5 GM118975","5RL5GM118975-03"],"pubmed_authors":["McCarley A","Espejo ML","Cooper KK","Ruiz C","Harmon DE"],"additional_accession":[]},"is_claimable":false,"name":"Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen Cupriavidus gilardii.","description":"The Gram-negative bacterium <i>Cupriavidus gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> strains sequenced to date. The intrinsic resistome of <i>C. gilardii</i> did not include the colistin resistance gene <i>mcr-5</i>, which was in a transposon present only in one strain. The intrinsic resistome of <i>C. gilardii</i> was comprised of (i) many multidrug efflux pumps, such as a homolog of the <i>Pseudomonas aeruginosa</i> 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-<i>N</i>-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 <i>C. gilardii</i> to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy.<b>IMPORTANCE</b><i>Cupriavidus gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> 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 <i>C. gilardii</i> strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Oct","modification":"2026-06-16T05:04:35.775Z","creation":"2019-11-05T08:11:46Z"},"accession":"S-EPMC6796972","cross_references":{"pubmed":["31578249"],"doi":["10.1128/mSphere.00631-19"]}}