Multidrug-Resistant Streptococcus agalactiae Strains Found in Human and Fish with High Penicillin and Cefotaxime Non-Susceptibilities.

Carmen Li,Margaret Ip,Dulmini Sapugahawatte,Norman Lo,Ying Yang,Kam Wong

doi:10.3390/microorganisms8071055

Abstract

Penicillin non-susceptible Streptococcus agalactiae (PEN-NS GBS) has been increasingly reported, with multidrug-resistant (MDR) GBS documented in Japan. Here we identified two PEN-NS GBS strains during our surveillance studies: one from a patient’s wound and the other from a tilapia. The patient’s GBS (H21) and fish GBS (F49) were serotyped and tested for antibiotic susceptibility. Whole-genome sequencing was performed to find the sequence type, antimicrobial resistance genes, and mutations in penicillin-binding proteins (PBPs) and fluoroquinolone (FQ) resistance genes. H21 and F49 belonged to ST651, serotype Ib, and ST7, serotype Ia, respectively. H21 showed PEN and cefotaxime minimum inhibitory concentrations (MICs) of 2.0 mg/L. F49 showed PEN MIC 0.5 mg/L. H21 was MDR with ermB, lnuB, tetS, ant6-Ia, sat4a, and aph3-III antimicrobial resistance genes observed. Alignment of PBPs showed the combination of PBP1B (A95D) and 2B mutations (V80A, S147A, S160A) in H21 and a novel mutation in F49 at N192S in PBP2B. Alignment of FQ-resistant determinants revealed mutation sites on gyrA, gyrB, and parC and E in H21. To our knowledge, this is the first report of GBS isolates with such high penicillin and cefotaxime MICs. This raises the concern of emergence of MDR and PEN-NS GBS in and beyond healthcare facilities.

Highlights

Group B Streptococcus (GBS) is a normal commensal of the genitourinary tract as well as a major pathogenic organism of invasive infections in neonates, pregnant women, non-pregnant adults including those with underlying diseases [1]
We have recently identified two GBS strains with Penicillin G (PEN)-NS, one from a patient (H21) during our surveillance studies on human carriage isolates and one from a tilapia fish (F49) during our food surveillance study
Lack of protein prediction analysis and functional assays of the penicillin-binding proteins (PBPs) substitutions to pinpoint the relation of these mutations to raised PEN minimum inhibitory concentrations (MICs) is a limitation of our study, especially in PBP2B, where the mutations were at two serine sites, a common amino acid found in catalytic sites

Summary

Introduction

Group B Streptococcus (GBS) is a normal commensal of the genitourinary tract as well as a major pathogenic organism of invasive infections in neonates, pregnant women, non-pregnant adults including those with underlying diseases (e.g., diabetics) [1]. GBS causes infections in animals, including bovine mastitis and streptococcosis in farmed fish, which jeopardizes farm production [2,3]. Penicillins and aminopenicillins, are recommended as first-line therapy against GBS infections; macrolides (erythromycin) and lincosamide (clindamycin) represent the second-line antibiotics that are usually prescribed for those with an allergy to beta-lactams. Penicillin G (PEN) is the drug of choice and is used widely in treatment and prevention of GBS infection, such as intrapartum antibiotic prophylaxis in pregnant mothers to prevent early onset GBS neonatal disease [5]. Penicillin non-susceptibility (PEN-NS) is an important concern and may necessitate alternative options in treatment guidelines

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