Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in β-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan

Abstract

Objectiveβ-Lactamase-negative ampicillin-resistant Haemophilus influenzae is a common opportunistic pathogen of hospital- and community-acquired infections, harboring multiple single nucleotide polymorphisms in the ftsI gene, which codes for penicillin-binding protein-3. The objectives of this study were to perform comprehensive genetic analyses of whole regions of the penicillin-binding proteins in H. influenzae and to identify additional single nucleotide polymorphisms related to antibiotic resistance, especially to ampicillin and other cephalosporins.ResultsIn this genome analysis of the ftsI gene in 27 strains of H. influenzae, 10 of 23 (43.5%) specimens of group III genotype β-lactamase-negative ampicillin-resistant H. influenzae were paradoxically classified as ampicillin-sensitive phenotypes. Unfortunately, we could not identify any novel mutations that were significantly associated with ampicillin minimum inhibitory concentrations in other regions of the penicillin-binding proteins, and we reconfirmed that susceptibility to β-lactam antibiotics was mainly defined by previously reported SNPs in the ftsI gene. We should also consider detailed changes in expression that lead to antibiotic resistance in the future because the acquisition of resistance to antimicrobials can be predicted by the expression levels of a small number of genes.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3169-0) contains supplementary material, which is available to authorized users.

Resistance Determinants and Their Genetic Context in Enterobacteria from a Longitudinal Study of Pigs Reared under Various Husbandry Conditions

“…Two penicillin-binding proteins emerged as major determinants for resistance to ampicillin and first- and third-generation cephalosporins. These included a variant of PBP3 initially discovered in Haemophilus influenzae ( 43 ) described as a pivotal component of the cell division complex ( 44 ) and AmpH, which is involved in peptidoglycan recycling ( 45 ). Chromosomally encoded AmpC proteins were the first enzymes reported to degrade penicillin ( 46 ) and conferred resistance to ampicillin, 1GC, and 3GC.…”

Extended-Spectrum β-Lactamases in Human Isolates of Multidrug-Resistant Non-typhoidal Salmonella enterica

“…Initially we identified the genes of resistance to β-lactam antibiotics in 19 ESBL-producers compared to 17 ESBL-negative isolates. The same amino acid substitutions S357N and D350N in PBP3 encoded by the ftsI gene ( Misawa et al, 2018 ), were found in all MDR NTS isolates, regardless of the ESBL-production phenotype. Interestingly, four strains with these substitutions were sensitive to all β-lactams tested.…”

“…As determined by bioinformatics analysis of WGS data, all 19 ESBL-positive isolates possessed the common β-lactam resistance mechanisms. According to CARD, these included the bla CTX–M– 5 gene and two amino acid substitutions, S357N and D350N, in penicillin binding protein 3 (PBP3), which is encoded by the ftsI gene ( Misawa et al, 2018 ) ( Table 2 ). In four isolates (4/19, 21.05%), in addition to the common β-lactam resistance mechanisms, the bla OXA– 1 gene was identified.…”

Identification of Primary Antimicrobial Resistance Drivers in Agricultural Nontyphoidal Salmonella enterica Serovars by Using Machine Learning

“…2). Every isolate had a pair of fosfomycin resistance-related mutations in the glpT and uhpT transporters (21) as well as a pmrF gene associated with resistance to polymyxin antibiotics (22), a Penicillin-binding protein (PBP) 3 gene (23), and a bacA gene (associated with low-level resistance to bacitracin) (24). Additionally, there were 16 efflux components and determinants associated with their expression, including general efflux regulators such as H-NS histone-like protein (25) and cpxA (26).…”