Occurrence and Variability of the Efflux Pump Gene norA across the Staphylococcus Genus

Abstract

NorA is one of the main native MDR efflux pumps of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides, but little is known about its variability within S. aureus or its distribution and conservation among other staphylococci. We screened for sequences homologous to S. aureus norA and found it in 61 out of the 63 Staphylococcus species described. To the best of our knowledge, this is the first study to report the occurrence of norA across the Staphylococcus genus. The norA phylogenetic tree follows the evolutionary relations of staphylococci and the closely related Mammalliicoccus genus. Comparative analyses suggest a conservation of the NorA function in staphylococci. We also analyzed the variability of norA within S. aureus, for which there are several circulating norA alleles, differing up to 10% at the nucleotide level, which may hamper proper norA detection. We demonstrate the applicability of a PCR-based algorithm to detect and differentiate norA alleles in 52 S. aureus representing a wider collection of 89 isolates from different hosts. Our results highlight the prevalence of norAI and norAII in different settings and the association of norA alleles with specific S. aureus clonal lineages. Ultimately, it confirms the applicability of our PCR-based algorithm to rapidly detect and assign the different norA alleles, a trait that may impact antimicrobial efflux capacity and the search for potential NorA inhibitors.

Antibiotic Resistance/Susceptibility Profiles of Staphylococcus equorum Strains from Cheese, and Genome Analysis for Antibiotic Resistance Genes

“…As regards erythromycin resistance, the simultaneous presence of msr(A) and mph(C) in a single strain, as might be the case in some of the present strains, has previously been associated with enhanced MICs [61]. norA encodes an efflux pump of the major facilitator superfamily that has been associated with resistance to fluoroquinolones in Staphylococcus [62]. However, this gene in the S. equorum strains of this study was not associated with ciprofloxacin resistance.…”

Antibiotic Resistance/Susceptibility Profiles of <em>Staphylococcus equorum </em>Strains from Cheese, and Genome Analysis for Antibiotic Resistance Genes

“…As regards erythromycin resistance, the simultaneous presence of msr(A) and mph(C) in a single strain, as might be the case in some of the present strains, has previously been associated with enhanced MICs [43]. norA encodes an efflux pump of the major facilitator superfamily that has been associated with resistance to fluoroquinolones in Staphylococcus [44]. However, this gene in the S. equorum strains was not associated with ciprofloxacin resistance.…”

“…Finally, although the MICs for ciprofloxacin were low, database searches identified a polymorphic norA gene in all strains (Figure S5C). This chromosomal gene codes for a housekeeping efflux pump of the major facilitator superfamily (MFS) known to be involved in fluoroquinolone resistance in the Staphylococcus genus [44]. a Identity and coverage of DNA or protein sequence, depending on the database.…”

Dendritic cells: the yin and yang in disease progression

“…CD103 + DC subsets with high expression of PD-L1/2 could be induced by the deficiency of the Smad7 protein, a negative regulator of TGF-β signaling ( 129 ). Also, CD103 + DCs have a colitogenic role and show impaired ability to produce Tregs ( 130 ) but generate Th1/Th2/Th17 responses through the induction of a huge variety of cytokines, including IFN-γ, IL-13, IL-6, IL-23, IL-12p35, IL-12p40, and TNF ( 131 – 133 ). The CD83 expression in DCs have also been found in IBD patients ( 134 ).…”