Prevalence and molecular characterization of methicillin-resistant Staphylococcus aureus with mupirocin, fusidic acid and/or retapamulin resistance

BMC Microbiol. 2020 Jun 29;20(1):183. doi: 10.1186/s12866-020-01862-z.

Abstract

Background: The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).

Results: Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates.

Conclusions: MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.

Keywords: Fusidic acid; Genetic characteristics; Methicillin-resistant Staphylococcus aureus; Mupirocin; Resistance mechanisms; Retapamulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Typing Techniques
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • China / epidemiology
  • DNA, Bacterial / genetics
  • Diterpenes / pharmacology
  • Drug Resistance, Multiple, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Fusidic Acid / pharmacology
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / classification*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Mupirocin / pharmacology
  • Mutation
  • Prevalence
  • Sequence Analysis, DNA
  • Staphylococcal Infections / epidemiology*

Substances

  • Anti-Bacterial Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • DNA, Bacterial
  • Diterpenes
  • retapamulin
  • Fusidic Acid
  • Mupirocin