scholarly journals Sublethal β-lactam antibiotics induce PhpP phosphatase expression and StkP kinase phosphorylation in PBP-independent β-lactam antibiotic resistance ofStreptococcus pneumoniae

2018 ◽  
Author(s):  
Yan-Ying Huang ◽  
Yan-Hong Sun ◽  
Peng Du ◽  
Xiao-Xiang Liu ◽  
Jie Yan ◽  
...  

AbstractStkP and PhpP ofStreptococcus pneumoniaehave been confirmed to compose a signaling couple, in which the former is a serine/threonine (Ser/Thr) kinase while the latter was annotated as a phosphotase. StkP has been reported to be involved in penicillin-binding protein (PBP)-independent penicillin resistance ofS. pneumoniae. However, the enzymatic characterization of PhpP and the role of PhpP in StkP-PhpP couple remain poorly understood. Here we showed that 1/4 minimal inhibitory concentration (MIC) of penicillin (PCN) or cefotaxime (CTX), the representatives of β-lactam antibiotics, could induce the expression ofstkPandphpPgenes and phosphorylation of StkP in PCN/CTX-sensitive strain ATCC6306 and three isolates ofS. pneumoniae(MICs: 0.02-0.5 μg/ml). The product ofphpPgene hydrolyzed PP2C type Ser/Thr phosphotase-specific RRA(pT)VA phosphopeptide substrate with the Km and Kcat values of 277.35 μmol/L and 0.71 S−1, and the hydrolytic activity was blocked by sodium fluoride, a PP2C type Ser/Thr phosphatase inhibitor. The phosphorylation levels of StkP in the fourphpPgene-knockout (ΔphpP) mutants were significantly higher than that in the wild-type strains. In particular, the MICs of PCN and CTX against the ΔphpPmutants were significantly elevated as 4-16 μg/ml. Therefore, our findings confirmed that sublethal PCN and CTX act as environmental inducers to cause the increase ofphpPandstkPgene expression and StkP phosphorylation. PhpP is a PP2C type Ser/Thr protein phosphatase responsible for dephosphorylation of StkP. Knockout of thephpPgene results in a high level of StkP phosphorylation and PBP-independent PCN/CTX resistance ofS. pneumoniae.ImportanceStreptococcus pneumoniaeis a common pathogen in human populations in many countries and areas due to the prevalence of β-lactam antibiotic-resistant pneumococcal strains. Production of β-lactamases and mutation of penicillin-binding proteins (PBP) have been considered as the major β-lactam antibiotic-resistant mechanisms in bacteria, butS. pneumoniaehas not been confirmed to produce any β-lactamases and many pneumococcal strains present PBP mutation-independent β-lactam antibiotic resistance. StkP is a Ser/Thr kinase ofS. pneumoniaeto compose a signal-couple with PhpP protein. The present study demonstrated that the PhpP is a PP2C-type phosphotase for dephosphorylation of StkP and the sublethal penicillin (PCN) or cefotaxime (CTX) acted as environmental signal molecules to induce the expression of PhpP. The knockout of PhpP-encoding gene caused the PCN/CTX resistance generation of PCN/CTX-sensitive pneumococcal strains. All the data indicate that StkP-PhpP couple ofS. pneumoniaeis involved in PBP mutation-independent β-lactam antibiotic resistance by phosphorylation of StkP.

2002 ◽  
Vol 15 (4) ◽  
pp. 647-679 ◽  
Author(s):  
José L. Martínez ◽  
Fernando Baquero

SUMMARY Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.


Author(s):  
E.A. Kolesnikova ◽  
N.F. Brusnigina ◽  
G.I. Grigor’eva

Urogenital mycoplasmas (Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma spp.) currently prevail in the etiology of infections of the urogenital tract and are characterized by a high level of genetic polymorphism responsible for the occurrence of their antibiotic resistance. The review presents the data of domestic and foreign researchers on the resistance mechanisms of mycoplasmas and ureaplasmas to antibiotics and considers the acquisition by mycoplasmas of antibiotic resistance determinants. New knowledge of resistance mechanisms is important theoretical basis for improving measures to limit and prevent the spread of antibiotic resistant bacteria.


1996 ◽  
Vol 40 (9) ◽  
pp. 2190-2193 ◽  
Author(s):  
A E Simor ◽  
M Louie ◽  
D E Low

The antimicrobial susceptibilities of 1,089 clinical isolates of Streptococcus pneumoniae obtained from 39 laboratories across Canada between October 1994 and August 1995 were determined. A total of 91 isolates (8.4%) demonstrated intermediate resistance (MIC, 0.1 to 1.0 microgram/ml) and 36 (3.3%) had high-level resistance (MIC, > or = 2.0 micrograms/ml) to penicillin. Penicillin-resistant strains were more likely to have been recovered from normally sterile sites (P = 0.005) and to be cross-resistant to several beta-lactam and non-beta-lactam antimicrobial agents (P < 0.05). These results indicate that there has been a recent significant increase in the prevalence of antibiotic-resistant S. pneumoniae in Canada.


Author(s):  
Natalia M. Alyabyeva ◽  
Ekaterina A. Brzhozovskaya ◽  
Olga A. Ponomarenko ◽  
Anna V. Lazareva ◽  
Andrey P. Fisenko

Introduction. The formation and spread of antibiotic-resistant Streptococcus pneumoniae isolates is a concern. After the thirteen-valent pneumococcal conjugate vaccine (PCV13) was added to the children’s immunization program in Russia in 2014, an important task is to monitor the resistance level to antimicrobials and the spectrum of circulating antibiotic-resistant pneumococcal serotypes. Materials and methods. The study included 708 nasopharyngeal pneumococcal isolates from children patients under 5 years who recovered from 2010 to 2018, received inpatient and outpatient care at the National Medical Research Center for Children’s Health (Moscow). The determination of sensitivity to antimicrobials was performed by the disk diffusion method. The MICs of penicillin, amoxicillin, and erythromycin were determined using the E-test method. Evaluation of the results was carried out according to the EUCAST-2019 criteria. Results. In total, 33 different serotypes were identified in the S. pneumoniae collection. Six predominant serotypes accounted for 68.6% of the total distribution and included serotypes: 19F, 6B, 23F, 14, 15B/C, 6A. In general, antimicrobial resistance ranged from 3.5% to chloramphenicol to 54.8% to tetracycline. The level of resistance to oxacillin, erythromycin, and clindamycin increased by 15-20% between 2010 and 2018. However, since 2016, there has established a prevalence level of 40-46%, this process is offset by an increase in the proportion of non-vaccine pneumococcal serotypes. Conclusion. A high level of resistance to penicillin and erythromycin remains. Monitoring the resistance level to antibiotics and the epidemiology of serotypes, clarifying the laws of formation of resistance, and its spread in a dynamically changing pneumococcal population is an important area of microbiology.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Izabela Korona-Glowniak ◽  
Radoslaw Siwiec ◽  
Anna Malm

Multiple resistance ofStreptococcus pneumoniaeis generally associated with their unique recombination-mediated genetic plasticity and possessing the mobile genetic elements. The aim of our study was to detect antibiotic resistance determinants and conjugative transposons in 138 antibiotic-resistant pneumococcal strains isolated from nasopharynx of healthy young children from Lublin, Poland. These strains resistant to tetracycline and/or to chloramphenicol/erythromycin/clindamycin were tested by PCR using the specific genes as markers. The presence of Tn916family transposons, carryingtet(M) andint/xisTn916, was observed in all of the tested strains. Tn916was detected in 16 strains resistant only to tetracycline. Tn6002and Tn3872-related element were found among 99erm(B)-carrying strains (83.8% and 3.0%, resp.). Eight strains harbouringmef(E) anderm(B) genes were detected, suggesting the presence of Tn2010and Tn2017transposons. Among 101 chloramphenicol-resistant strains, two variants of Tn5252-related transposon were distinguished depending on the presence ofint/xis5252genes specific forcatgene-containing Tn5252(75.2% of strains) orintSp23FST81gene, specific forcat-containing ICESp23FST81 element (24.8% of strains). In 6 strains Tn916-like and Tn5252-like elements formed a Tn5253-like structure. Besides clonal dissemination of resistant strains of pneumococci in the population, horizontal transfer of conjugative transposons is an important factor of the high prevalence of antibiotic resistance.


mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Alin Finkelshtein ◽  
Dalit Roth ◽  
Eshel Ben Jacob ◽  
Colin J. Ingham

ABSTRACTSwarming bacteria are challenged by the need to invade hostile environments. Swarms of the flagellated bacteriumPaenibacillus vortexcan collectively transport other microorganisms. Here we show thatP. vortexcan invade toxic environments by carrying antibiotic-degrading bacteria; this transport is mediated by a specialized, phenotypic subpopulation utilizing a process not dependent on cargo motility. Swarms of beta-lactam antibiotic (BLA)-sensitiveP. vortexused beta-lactamase-producing, resistant, cargo bacteria to detoxify BLAs in their path. In the presence of BLAs, both transporter and cargo bacteria gained from this temporary cooperation; there was a positive correlation between BLA resistance and dispersal.P. vortextransported only the most beneficial antibiotic-resistant cargo (including environmental and clinical isolates) in a sustained way.P. vortexdisplayed a bet-hedging strategy that promoted the colonization of nontoxic niches byP. vortexalone; when detoxifying cargo bacteria were not needed, they were lost. This work has relevance for the dispersal of antibiotic-resistant microorganisms and for strategies for asymmetric cooperation with agricultural and medical implications.IMPORTANCEAntibiotic resistance is a major health threat. We show a novel mechanism for the local spread of antibiotic resistance. This involves interactions between different bacteria: one species provides an enzyme that detoxifies the antibiotic (a sessile cargo bacterium carrying a resistance gene), while the other (Paenibacillus vortex) moves itself and transports the cargo.P. vortexused a bet-hedging strategy, colonizing new environments alone when the cargo added no benefit, but cooperating when the cargo was needed. This work is of interest in an evolutionary context and sheds light on fundamental questions, such as how environmental antibiotic resistance may lead to clinical resistance and also microbial social organization, as well as the costs, benefits, and risks of dispersal in the environment.


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