Abstract
Background
Multidrug efflux pumps (MDR EPs) play a major role in the emergence of antimicrobial resistance (AMR). NorA is one of the main native MDR EPs of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides[1,2]. In S. aureus, its gene occurs in several allelic variants[3], but less is known about the occurrence of norA and other MDR EPs across the Staphylococcus genus. In this work, we analyze the
presence of norA across staphylococci and identify other main MDR EP determinants in four additional pathogenic staphylococcal species.
Methods
The norA nucleotide sequences from 61 Staphylococcus species were retrieved from public databases and aligned. The corresponding predicted polypeptide sequences were also aligned and the impact of possible residue substitutions on NorA activity was analyzed. Other MDR
EP genes were searched in public databases for Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis and Staphylococcus hominis. Additionally, sequences homologues to S. aureus norB/C, sdrM, lmrS, mepA and mdeA were screened by BLAST search in the complete genome of representative strains of each species.
Results
The norA phylogenetic tree follows the evolutionary relations of the Staphylococcus genus highlighting the presence of norA in the early branching of the genus. Comparative analyses suggest a conservation of NorA function in staphylococci. Over 30 putative MDR EP genes were identified for S. epidermidis, S. haemolyticus and S. lugdunensis. Homologues of S. aureus norB/C and sdrM were identified in both S. epidermidis and S. hominis,
while mepA and mdeA were only detected in S. hominis and lmrS in S. epidermidis.
Conclusions
Our results suggest an overall conservation of NorA function across staphylococci, indicating that norA is part of the staphylococcal core genome. The identification of main MDR EP determinants in other staphylococcal species of clinical relevance opens new avenues for the study of their impact on AMR.
Project BIOSAFE funded by FEDER through the Programa Operacional Factores de Competitividade—COMPETE and by Fundação para a Ciência e a Tecnologia (FCT, Portugal)— Grants LISBOA-01-0145-FEDER-030713, PTDC/CAL-EST/30713/2017, 2021.05063.BD and UID/04413/2020
Multidrug efflux pumps (MDR EPs) play a major role in the emergence of antimicrobial resistance (AMR). NorA is one of the main native MDR EPs of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides[1,2]. In S. aureus, its gene occurs in several allelic variants[3], but less is known about the occurrence of norA and other MDR EPs across the Staphylococcus genus. In this work, we analyze the
presence of norA across staphylococci and identify other main MDR EP determinants in four additional pathogenic staphylococcal species.
Methods
The norA nucleotide sequences from 61 Staphylococcus species were retrieved from public databases and aligned. The corresponding predicted polypeptide sequences were also aligned and the impact of possible residue substitutions on NorA activity was analyzed. Other MDR
EP genes were searched in public databases for Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdunensis and Staphylococcus hominis. Additionally, sequences homologues to S. aureus norB/C, sdrM, lmrS, mepA and mdeA were screened by BLAST search in the complete genome of representative strains of each species.
Results
The norA phylogenetic tree follows the evolutionary relations of the Staphylococcus genus highlighting the presence of norA in the early branching of the genus. Comparative analyses suggest a conservation of NorA function in staphylococci. Over 30 putative MDR EP genes were identified for S. epidermidis, S. haemolyticus and S. lugdunensis. Homologues of S. aureus norB/C and sdrM were identified in both S. epidermidis and S. hominis,
while mepA and mdeA were only detected in S. hominis and lmrS in S. epidermidis.
Conclusions
Our results suggest an overall conservation of NorA function across staphylococci, indicating that norA is part of the staphylococcal core genome. The identification of main MDR EP determinants in other staphylococcal species of clinical relevance opens new avenues for the study of their impact on AMR.
Project BIOSAFE funded by FEDER through the Programa Operacional Factores de Competitividade—COMPETE and by Fundação para a Ciência e a Tecnologia (FCT, Portugal)— Grants LISBOA-01-0145-FEDER-030713, PTDC/CAL-EST/30713/2017, 2021.05063.BD and UID/04413/2020
| Original language | English |
|---|---|
| Publication status | Published - 18 Apr 2023 |
| Event | 33rd European Congress of Clinical Microbiology and Infectious Diseases - Copenhagen, Denmark Duration: 15 Apr 2023 → 18 Apr 2023 |
Conference
| Conference | 33rd European Congress of Clinical Microbiology and Infectious Diseases |
|---|---|
| Abbreviated title | 33rd ECCMID |
| Country/Territory | Denmark |
| City | Copenhagen |
| Period | 15/04/23 → 18/04/23 |
Keywords
- Antimicrobial resistance
- genomics and metagenomics
- Efflux
