PXD042287

PXD042287 is an original dataset announced via ProteomeXchange.

Title	Transcriptomics and mutagenesis analysis uncover key mechanisms involved in polymyxin B resistance and heteroresistance of the neonatal sepsis pathogen Enterobacter bugandensis
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:35:11.280.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nichollas Scott
SpeciesList	scientific name: Enterobacter bugandensis; NCBI TaxID: 881260;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-17 05:56:14	ID requested
1	2024-04-04 17:25:36	announced
⏵ 2	2024-10-22 06:35:12	announced	2024-10-22: Updated project metadata.

Garc, í, a-Romero I, Srivastava M, Monjar, á, s-Feria J, Korankye SO, MacDonald L, Scott NE, Valvano MA, Drug efflux and lipid A modification by 4-L-aminoarabinose are key mechanisms of polymyxin B resistance in the sepsis pathogen Enterobacter bugandensis. J Glob Antimicrob Resist, 37():108-121(2024) [pubmed]

10.1016/j.jgar.2024.03.012;

submitter keyword: Enterobacter bugandensis, polymyxin B resistance

Miguel A. Valvano
contact affiliation	Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, BT9 7BL
contact email	m.valvano@qub.ac.uk
lab head
Nichollas Scott
contact affiliation	University of Melbourne
contact email	nichollas.scott@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042287
     1. Label: PRIDE project
     2. Name: Transcriptomics and mutagenesis analysis uncover key mechanisms involved in polymyxin B resistance and heteroresistance of the neonatal sepsis pathogen Enterobacter bugandensis