Dataset Information

Transcriptomics and mutagenesis analysis uncover key mechanisms involved in polymyxin B resistance and heteroresistance of the neonatal sepsis pathogen Enterobacter bugandensis

ABSTRACT: Enterobacter bugandensis is one of species from the E. cloacae complex (ECC) that has been predominantly associated to neonatal sepsis. A major concern with E. bugandensis and ECC bacteria in general is the frequent appearance of multidrug resistant isolates including those resistant to last-resort antibiotics, such as polymyxins, for which these microbes are in the ESKAPE list of global threat pathogens. Here, we investigated polymyxin B (PmB) resistance and heteroresistance in E. bugandensis by transcriptomics and a gene deletion approach using two clinical isolates. Genes encoded in the CrrAB-regulated operon including crrC and kexD were highly upregulated in both strains in the presence of PmB. We show in one of these isolates that ∆crrC and ∆kexD mutants exhibited lower levels of PmB resistance and heteroresistance than the parental strain. Moreover, the heterologous expression of CrrC and KexD proteins increased PmB resistance in a sensitive E. ludwigii clinical isolate and in the Escherichia coli K12 strain W3110. We also showed that the efflux pump AcrAB and TolC contribute to PmB resistance and heteroresistance. Deletion of the regulatory genes phoPQ and crrAB cause reduced PmB resistance and heteroresistance, while deletion of pmrAB did not have any effect. Our results also reveal that the addition of L-Ara4N into the lipid A, mediated by the arnBCADTEF operon, is critical to determine PmB resistance, while the deletion of eptA, encoding a PEtN transferase had no effect. Finally, PmB resistance did not correlate with pathogenicity in the Galleria mellonella infection model.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Enterobacter Bugandensis

SUBMITTER: Nichollas Scott

LAB HEAD: Miguel A. Valvano

PROVIDER: PXD042287 | Pride | 2024-04-05

REPOSITORIES: pride

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Dataset's files

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			Action	DRS
	221208_NSco-5557_MV_gel_sample1.raw	Raw
	221208_NSco-5557_MV_gel_sample10.raw	Raw
	221208_NSco-5557_MV_gel_sample10_-45.mzXML	Mzxml
	221208_NSco-5557_MV_gel_sample10_-65.mzXML	Mzxml
	221208_NSco-5557_MV_gel_sample11.raw	Raw

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Publications

Drug efflux and lipid A modification by 4-L-aminoarabinose are key mechanisms of polymyxin B resistance in the sepsis pathogen Enterobacter bugandensis.

García-Romero Inmaculada I Srivastava Mugdha M Monjarás-Feria Julia J Korankye Samuel O SO MacDonald Lewis L Scott Nichollas E NE Valvano Miguel A MA

Journal of global antimicrobial resistance 20240327

<h4>Objectives</h4>A concern with the ESKAPE pathogen, Enterobacter bugandensis, and other species of the Enterobacter cloacae complex, is the frequent appearance of multidrug resistance against last-resort antibiotics, such as polymyxins.<h4>Methods</h4>Here, we investigated the responses to polymyxin B (PMB) in two PMB-resistant E. bugandensis clinical isolates by global transcriptomics and deletion mutagenesis.<h4>Results</h4>In both isolates, the genes of the CrrAB-regulated operon, includin ...[more]

PMID: 38552872

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