Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China

Abstract

Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

Analysis of amino acid motif of penicillin-binding proteins 1a, 2b, and 2x in invasive Streptococcus pneumoniae nonsusceptible to penicillin isolated from pediatric patients in Casablanca, Morocco

“…Previous studies have suggested that PBP1a, − 2x, and − 2b are generally recognized as the major PBPs associated with the activities of penicillins and some cephalosporins [ 4 , 12 ]. In our study, changes found in PBP1A, PBP2b and PBP2X are globally similar to those previously reported [ 6 , 13 , 14 ].…”

“…The maximal level of resistance of PNSP responsible of invasive pneumococcal disease reported in Casablanca, is relatively low with the maximal MICs = 2 mg/L compared to MICs of PNSP in many countries where MICs ≥ 8 mg/L were reported [ 14 , 15 ]. Our investigation of the PBP1a, − 2x, and − 2b amino acid sequences of 30 clinical pneumococci demonstrates that the degree of diversity within these amino acid sequences correlates with increasing resistance to β-lactam antibiotics.…”

Molecular characterization of penicillin non-susceptible Streptococcus pneumoniae isolated before and after pneumococcal conjugate vaccine implementation in Casablanca, Morocco

“…Significant reduction of PNSP occurred in several countries after the use of PCV [19–23]. The maximal level of resistance of PNSP responsible of IPD is relatively low with MICs = 2 mg/L compared to MICs of PNSP in many countries where MICs ≥ 8 mg/L were reported [4, 24]. Serotypes among PNSP were mainly 6B, 14, 19A, 19F and 23F in children and adults.…”

“…Pneumococcal resistance to β-lactams has been attributed to alterations of the penicillin-binding proteins (PBP) which reduce their affinity [4]. The first pneumococcal isolate resistant to penicillin was reported in 1967 from a patient in Australia [5], and resistant pneumococci have subsequently increased in prevalence worldwide.…”

“…Vaccination has also reduced the incidence rate of antibiotic resistant serotypes, but we previously reported, a rebound due to the persistence of some vaccine serotypes like 6B and 14 [11]. Although several studies have described the genetic profile of the pbp1a , pbp2b and pbp2x genes in pneumococci from different countries [4, 13], actually, there are no studies on the characteristics of penicillin non- susceptible S. pneumoniae (PNSP) in Morocco.…”