Penicillin- and Cephalosporin-Resistant Streptococcus pneumoniae: An Emerging Microbial Threat

PEDIATRICS ◽  
1994 ◽  
Vol 93 (3) ◽  
pp. 500-503 ◽  
Author(s):  
Robert J. Leggiadro
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Disease ◽  
Inhibitory Concentration ◽  
Penicillin Resistance ◽  
Cell Wall Synthesis ◽  
Penicillin Binding Proteins ◽  
Clinical Challenge ◽  
Recent Developments ◽  
High Level ◽  
Level Resistance

Recent reports from South Africa,1 Spain,2 Hungary,3 Texas,4-6 and Memphis7,8 document an increasing incidence of penicillin-resistant Streptococcus pneumoniae infections in children. The emergence of penicillin-resistant pneumococci that also demonstrate decreased susceptibility to extended-spectrum cephalosporins presents an even greater clinical challenge.6-9 This commentary reviews recent developments in the epidemiology, identification, and management of penicillin- and cephalosporin-resistant pneumococcal disease in children. Pneumococcal susceptibility to penicillin is defined as a minimal inhibitory concentration (MIC) <0.1 µg/mL. Intermediate (relative) penicillin resistance is defined as an MIC from 0.1 to 1.0 µg/mL and high-level resistance as an MIC >1.0 µ/mL. Pneumococcal penicillin resistance is mediated by alterations in penicillin-binding proteins involved in cell wall synthesis.10

scholarly journals New Aspects of the Interplay between Penicillin Binding Proteins, murM, and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Inga Schweizer ◽  
Sebastian Blättner ◽  
Patrick Maurer ◽  
Katharina Peters ◽  
Daniela Vollmer ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Morphological Changes ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Two Component System ◽  
Gene Encoding ◽  
Content Type ◽  
Penicillin Binding Proteins ◽  
High Level

ABSTRACT The Streptococcus pneumoniae clone Hungary19A-6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232, encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104–3112, 2011, https://doi.org/10.1099/mic.0.053157-0 ). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary19A-6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x, pbp1a, murM, and ciaH, and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 (murM Hu17), which is highly similar to murM of Streptococcus mitis, induced morphological changes which were partly reversed by ciaH232. murM Hu17 conferred cefotaxime resistance only in the presence of the pbp2x of strain Hu17 (pbp2x Hu17). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2x Hu17 and pbp1a of strain Hu17 (pbp1a Hu17), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1aHu17-mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins.

Quintuplex PCR to Detect Antibiotic Resistance Genes in Streptococcus pneumoniae

2016 ◽  
Vol 1 (2) ◽  
pp. 22 ◽  
Author(s):  
Navindra Kumari Palanisamy ◽  
Parasakthi Navaratnam ◽  
Shamala Devi Sekaran
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Antibiotic Resistance Genes ◽  
Pcr Amplification ◽  
Penicillin Resistance ◽  
Penicillin Binding Proteins ◽  
Efflux Mechanism ◽  
Mic Value

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.

scholarly journals Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae

2002 ◽  
Vol 184 (20) ◽  
pp. 5619-5624 ◽  
Author(s):  
Wendy L. Veal ◽  
Robert A. Nicholas ◽  
William M. Shafer
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Base Pair ◽  
Efflux Pump ◽  
Penicillin Resistance ◽  
Single Base ◽  
Base Pair Deletion ◽  
Resistance To Penicillin ◽  
Single Base Pair ◽  
High Level ◽  
Level Resistance

ABSTRACT The importance of the mtrCDE-encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains of Neisseria gonorrhoeae was determined by using genetic derivatives of penicillin-sensitive strain FA19 bearing defined mutations (mtrR, penA, and penB) donated by a clinical isolate (FA6140) expressing high-level resistance to penicillin and antimicrobial hydrophobic agents (HAs). When introduced into strain FA19 by transformation, a single base pair deletion in the mtrR promoter sequence from strain FA6140 was sufficient to provide high-level resistance to HAs (e.g., erythromycin and Triton X-100) but only a twofold increase in resistance to penicillin. When subsequent mutations in penA and porIB were introduced from strain FA6140 into strain WV30 (FA19 mtrR) by transformation, resistance to penicillin increased incrementally up to a MIC of 1.0 μg/ml. Insertional inactivation of the gene (mtrD) encoding the membrane transporter component of the Mtr efflux pump in these transformant strains and in strain FA6140 decreased the MIC of penicillin by 16-fold. Genetic analyses revealed that mtrR mutations, such as the single base pair deletion in its promoter, are needed for phenotypic expression of penicillin and tetracycline resistance afforded by the penB mutation. As penB represents amino acid substitutions within the third loop of the outer membrane PorIB protein that modulate entry of penicillin and tetracycline, the results presented herein suggest that PorIB and the MtrC-MtrD-MtrE efflux pump act synergistically to confer resistance to these antibiotics.

scholarly journals Bacteremic Pneumonia Caused by Penicillin-Resistant Pneumococci: Case Report and Review with a Canadian Perspective

1992 ◽  
Vol 3 (4) ◽  
pp. 185-188
Author(s):  
David R Burdge ◽  
Vincent C Woo ◽  
Patricia MA Ritchie
Keyword(s):  
Antibiotic Resistance ◽  
Case Report ◽  
Streptococcus Pneumoniae ◽  
Minimal Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Penicillin Resistance ◽  
Sensitivity Testing ◽  
Antimicrobial Sensitivity ◽  
Canadian Perspective ◽  
Bacteremic Pneumonia

A Canadian adult with bacteremic pneumonia caused by a relatively penicillin-resistant (minimal inhibitory concentration 0.25 μg/mL) Streptococcus pneumoniae is reported, and the published literature regarding penicillin-resistant pneumococci in Canada reviewed. Although penicillin resistance has been reported infrequently to date, this case emphasizes the need for routine antimicrobial sensitivity testing of all pneumococci isolated from normally sterile sites, and for ongoing systematic surveillance for penicillin and other antibiotic resistance in Canada.

scholarly journals Capsule Homology Does Not Increase the Frequency of Transformation of Linked Penicillin Binding Proteins PBP 1a and PBP 2x in Streptococcus pneumoniae

2005 ◽  
Vol 49 (4) ◽  
pp. 1591-1592 ◽  
Author(s):  
Krzysztof Trzciński ◽  
Adam MacNeil ◽  
Keith P. Klugman ◽  
Marc Lipsitch
Keyword(s):  
Streptococcus Pneumoniae ◽  
Binding Proteins ◽  
Penicillin Resistance ◽  
Penicillin Binding Proteins ◽  
Transformation Rates

ABSTRACT Penicillin resistance is mainly confined to a limited number of Streptococcus pneumoniae serotypes. Given linkage between the capsular biosynthesis locus and two penicillin binding proteins, we tested whether capsule homology increases transformation rates of penicillin resistance. Transformation rates in homologous donor-recipient pairs were no higher than expected, falsifying this hypothesis.

scholarly journals Diversity of Substitutions within or Adjacent to Conserved Amino Acid Motifs of Penicillin-Binding Protein 2X in Cephalosporin-Resistant Streptococcus pneumoniaeIsolates

1999 ◽  
Vol 43 (5) ◽  
pp. 1252-1255 ◽  
Author(s):  
Yasuko Asahi ◽  
Yasuo Takeuchi ◽  
Kimiko Ubukata
Keyword(s):  
Streptococcus Pneumoniae ◽  
Amino Acid ◽  
Three Dimensional ◽  
Crystallographic Structure ◽  
Amino Acid Substitutions ◽  
Penicillin Binding Protein ◽  
Amino Acid Motif ◽  
Dna Fragment ◽  
High Level ◽  
Level Resistance

ABSTRACT The sequence of an approximately 1.1-kb DNA fragment of thepbp2x gene, which encodes the transpeptidase domain, was determined for 35 clinical isolates of Streptococcus pneumoniae for which the cefotaxime (CTX) MICs varied. Strains with substitutions within a conserved amino acid motif changing STMK to SAFK and a Leu-to-Val change just before the KSG motif were highly resistant to CTX (MIC, ≧2 μg/ml). Strains with substitutions adjacent to SSN or KSG motifs had low-level resistance. The amino acid substitutions were plotted on the three-dimensional crystallographic structure of the transpeptidase domain of PBP2X. Transformants containing pbp2x from strains with high-level CTX resistance increased the CTX MIC from 0.016 μg/ml to 0.5 to 1.0 μg/ml.

scholarly journals Hyper-Aerotolerant Campylobacter coli from Duck Sources and Its Potential Threat to Public Health: Virulence, Antimicrobial Resistance, and Genetic Relatedness

2019 ◽  
Vol 7 (11) ◽  
pp. 579 ◽  
Author(s):  
Jae-Ho Guk ◽  
Junhyung Kim ◽  
Hyokeun Song ◽  
Jinshil Kim ◽  
Jae-Uk An ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Inhibitory Concentration ◽  
Genetic Relatedness ◽  
Control Strategies ◽  
Campylobacter Coli ◽  
Potential Threat ◽  
High Level ◽  
Sequence Types ◽  
Level Resistance

Campylobacter, a common foodborne human pathogen, is considered sensitive to oxygen. Recently, aerotolerant (AT) Campylobacter jejuni with the ability to survive under aerobic stress has been reported. Here, we investigated the prevalence of hyper-aerotolerant (HAT) Campylobacter coli from duck sources (118 carcasses and meat) and its characteristics to assess potential impacts on public health. Half of 56 C. coli isolates were HAT and most harbored various virulence genes including flaA, cadF, cdtA, ceuB, and wlaN. Moreover, 98.2% of C. coli isolates showed resistance to quinolones, including ciprofloxacin (CIP), and nine (16.1%) showed high-level resistance to ciprofloxacin (Minimum Inhibitory Concentration, MIC ≥ 32 μg/mL) and most of these were HAT. Based on genetic relatedness between C. coli from duck sources and those from human sources (PubMLST and NCBI), HAT isolates sharing the same MLST sequence types were significantly more prevalent than those not sharing the same sequence types as those from human sources. Therefore, HAT C. coli is prevalent in duck sources, and is most likely transmitted to humans through the food chain given its aerotolerance. This being so, it might pose a threat to public health given its virulence and antimicrobial resistance (AMR). This study will assist in improving control strategies to reduce farm-to-table HAT C. coli transmission to humans.

scholarly journals Meningitis in a Canadian Adult due to High Level Penicillin-Resistant, Cefotaxime-IntermediateStreptococcus pneumoniae

1996 ◽  
Vol 7 (3) ◽  
pp. 205-207 ◽  
Author(s):  
Cécile Tremblay ◽  
Anne-Marie Bourgault ◽  
Pierre St-Antoine
Keyword(s):  
Streptococcus Pneumoniae ◽  
Adult Patient ◽  
Penicillin Resistance ◽  
High Level

Invasive penicillin-resistant pneumococcal (PRSP) infections are increasing worldwide. In Canada, the incidence of penicillin resistance amongStreptococcus pneumoniaeisolates is estimated at greater than 6%. In Quebec, only one case of PRSP meningitis has been reported and involved an infant. An adult patient is described who presented with meningitis caused by high level penicillin-resistant, cefotaxime-intermediateS pneumoniae.

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