scholarly journals Virulence genes and resistance to antibiotics of beta-hemolytic streptococci isolated from children in Chiapas, Mexico

2018 ◽  
Vol 12 (02) ◽  
pp. 80-88
Author(s):  
Javier Gutiérrez-Jiménez ◽  
Mónica Ivonne Mendoza-Orozco ◽  
Alejandra Vicente-Serrano ◽  
Lorena Mercedes Luna-Cazáres ◽  
José Manuel Feliciano-Guzmán ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Virulence Genes ◽  
Group A Streptococcus ◽  
Beta Lactams ◽  
Emerging Pathogens ◽  
First Line ◽  
Virulence Traits ◽  
Genes Encoding ◽  
Group A ◽  
Southeast Mexico

Introduction: Among beta-hemolytic streptococci, Streptococcus pyogenes causes a wide variety of human disease including pharyngitis, necrotizing fasciitis and streptococcal toxic syndrome. Group A Streptococcus (GAS) uses a variety of virulence traits to colonize and then cause damage to the host; others species of beta-hemolytic streptococci are considered as emerging pathogens for humans. Despite its recognized virulence, only few studies have investigated virulence factors of GAS strains isolated in Mexico. Methodology: We conducted an epidemiological study to investigate the prevalence of GAS strains in child illnesses in Chiapas Mexico. Virulence genes encoding proteases, DNases, superantigens, as well as susceptibility to antibiotics were investigated. Results: During 2010, 2013 and 2014, beta-hemolytic streptococci (N=12) were isolated from cases of bacterial infections including pharyngitis and bacteremia, with a prevalence of 0.42, 0.04 and 0.20%, respectively. S. pyogenes was the most frequent species (33%) followed by S. agalactiae and S. dysgalactiae subsp. equisimilis (25%, each). Most GAS strains encoded genes for proteases: scpA, speB, spyCEP and mac (75%), followed by sdaD and sdaB (DNases) (50%), speA and speG (superantigens; 50 and 25%, respectively). The scpA gene was amplified in all S. agalactiae strains and in ~35% of SDSE strains. Strains were all susceptible to beta-lactams, cephalosporins and quinolones. Conclusions: The present study provides evidence on the epidemiology of beta-hemolytic streptococci infecting children at the southeast Mexico, their virulence traits and sensitivity to first-line antibiotics.

scholarly journals Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A Streptococcus in the Oropharynx

2007 ◽  
Vol 75 (6) ◽  
pp. 2981-2990 ◽  
Author(s):  
Samuel A. Shelburne ◽  
Nnaja Okorafor ◽  
Izabela Sitkiewicz ◽  
Paul Sumby ◽  
David Keith ◽  
...  
Keyword(s):  
Parental Strain ◽  
Group A Streptococcus ◽  
Transcriptional Regulator ◽  
Human Saliva ◽  
Transcript Levels ◽  
Expression Of Genes ◽  
Rich Media ◽  
Genes Encoding ◽  
Group A ◽  
Mutant Derivative

ABSTRACT Group A Streptococcus (GAS) genes that encode proteins putatively involved in polysaccharide utilization show growth phase-dependent expression in human saliva. We sought to determine whether the putative polysaccharide transcriptional regulator MalR influences the expression of such genes and whether MalR helps GAS infect the oropharynx. Analysis of 32 strains of 17 distinct M protein serotypes revealed that MalR is highly conserved across GAS strains. malR transcripts were detectable in patients with GAS pharyngitis, and the levels increased significantly during growth in human saliva compared to the levels during growth in glucose-containing or nutrient-rich media. To determine if MalR influenced the expression of polysaccharide utilization genes, we compared the transcript levels of eight genes encoding putative polysaccharide utilization proteins in the parental serotype M1 strain MGAS5005 and its ΔmalR isogenic mutant derivative. The transcript levels of all eight genes were significantly increased in the ΔmalR strain compared to the parental strain, especially during growth in human saliva. Following experimental infection, the ΔmalR strain persistently colonized the oropharynx in significantly fewer mice than the parental strain colonized, and the numbers of ΔmalR strain CFU recovered were significantly lower than the numbers of the parental strain CFU recovered. These data led us to conclude that MalR influences the expression of genes putatively involved in polysaccharide utilization and that MalR contributes to the persistence of GAS in the oropharynx.

scholarly journals A Mobile Genetic Element Promotes the Association Between Serotype M28 Group A Streptococcus Isolates and Cases of Puerperal Sepsis

2019 ◽  
Vol 220 (5) ◽  
pp. 882-891 ◽  
Author(s):  
Ira Jain ◽  
Poulomee Sarkar ◽  
Jessica L Danger ◽  
Josette Medicielo ◽  
Roshika Roshika ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Reproductive Tract ◽  
Mobile Genetic Element ◽  
Group A Streptococcus ◽  
Female Reproductive Tract ◽  
Sequencing Analysis ◽  
Messenger Rnas ◽  
Genetic Element ◽  
Puerperal Sepsis ◽  
Group A

AbstractBackgroundBacterial infections following childbirth—so-called puerperal infections—cause morbidity in 5%–10% of all new mothers. At low frequency, the infection can spread to the blood, resulting in life-threatening sepsis known as puerperal sepsis. Pathogens causing puerperal sepsis include group A Streptococcus (GAS), and epidemiological analyses have identified isolates of a single serotype, M28, as being nonrandomly associated with cases of puerperal sepsis. The genomes of serotype M28 GAS isolates harbor a 36.3-kb mobile genetic element of apparent group B Streptococcus origin, termed region of difference 2 (RD2).MethodsThe phenotypic (determined via tissue culture and a vaginal colonization model) and regulatory (determined via RNA sequencing analysis) contributions of RD2 were assessed by comparing parental, RD2 deletion mutant, and complemented mutant serotype M28 GAS strains.ResultsRD2 affords serotype M28 isolates an enhanced ability to adhere to human vaginal epithelial cells and to colonize the female reproductive tract in a mouse model of infection. In addition, RD2 influences the abundance of messenger RNAs from >100 core chromosomal GAS genes.ConclusionsThe data are consistent with RD2 directly, via encoded virulence factors, and indirectly, via encoded regulatory proteins, modifying the virulence potential of GAS and contributing to the decades-old association of serotype M28 isolates with cases of puerperal sepsis.

scholarly journals Group A Streptococcus AdcR Regulon Participates in Bacterial Defense against Host-Mediated Zinc Sequestration and Contributes to Virulence

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Nishanth Makthal ◽  
Hackwon Do ◽  
Brian M. Wendel ◽  
Randall J. Olsen ◽  
John D. Helmann ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Group A Streptococcus ◽  
Zn Deficiency ◽  
Direct Competition ◽  
Mutant Strains ◽  
Genes Encoding ◽  
Group A ◽  
Gas Interactions

ABSTRACT Colonization by pathogenic bacteria depends on their ability to overcome host nutritional defenses and acquire nutrients. The human pathogen group A streptococcus (GAS) encounters the host defense factor calprotectin (CP) during infection. CP inhibits GAS growth in vitro by imposing zinc (Zn) limitation. However, GAS counterstrategies to combat CP-mediated Zn limitation and the in vivo relevance of CP-GAS interactions to bacterial pathogenesis remain unknown. Here, we report that GAS upregulates the AdcR regulon in response to CP-mediated Zn limitation. The AdcR regulon includes genes encoding Zn import (adcABC), Zn sparing (rpsN.2), and Zn scavenging systems (adcAII, phtD, and phtY). Each gene in the AdcR regulon contributes to GAS Zn acquisition and CP resistance. The ΔadcC and ΔrpsN.2 mutant strains were the most susceptible to CP, whereas the ΔadcA, ΔadcAII, and ΔphtD mutant strains displayed less CP sensitivity during growth in vitro. However, the ΔphtY mutant strain did not display an increased CP sensitivity. The varied sensitivity of the mutant strains to CP-mediated Zn limitation suggests distinct roles for individual AdcR regulon genes in GAS Zn acquisition. GAS upregulates the AdcR regulon during necrotizing fasciitis infection in WT mice but not in S100a9−/− mice lacking CP. This suggests that CP induces Zn deficiency in the host. Finally, consistent with the in vitro results, several of the AdcR regulon genes are critical for GAS virulence in WT mice, whereas they are dispensable for virulence in S100a9−/− mice, indicating the direct competition for Zn between CP and proteins encoded by the GAS AdcR regulon during infection.

scholarly journals d-Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

2005 ◽  
Vol 187 (19) ◽  
pp. 6719-6725 ◽  
Author(s):  
Sascha A. Kristian ◽  
Vivekanand Datta ◽  
Christopher Weidenmaier ◽  
Rita Kansal ◽  
Iris Fedtke ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Group A Streptococcus ◽  
Teichoic Acid ◽  
Systemic Infection ◽  
Human Neutrophils ◽  
Invasive Infection ◽  
Bacterial Surface ◽  
Innate Defense ◽  
Group A ◽  
Antimicrobial Peptide Resistance

ABSTRACT Group A streptococcus (GAS) is a leading cause of severe, invasive human infections, including necrotizing fasciitis and toxic shock syndrome. An important element of the mammalian innate defense system against invasive bacterial infections such as GAS is the production of antimicrobial peptides (AMPs) such as cathelicidins. In this study, we identify a specific GAS phenotype that confers resistance to host AMPs. Allelic replacement of the dltA gene encoding d-alanine-d-alanyl carrier protein ligase in an invasive serotype M1 GAS isolate led to loss of teichoic acid d-alanylation and an increase in net negative charge on the bacterial surface. Compared to the wild-type (WT) parent strain, the GAS ΔdltA mutant exhibited increased susceptibility to AMP and lysozyme killing and to acidic pH. While phagocytic uptake of WT and ΔdltA mutants by human neutrophils was equivalent, neutrophil-mediated killing of the ΔdltA strain was greatly accelerated. Furthermore, we observed the ΔdltA mutant to be diminished in its ability to adhere to and invade cultured human pharyngeal epithelial cells, a likely proximal step in the pathogenesis of invasive infection. Thus, teichoic acid d-alanylation may contribute in multiple ways to the propensity of invasive GAS to bypass mucosal defenses and produce systemic infection.

scholarly journals CovR Activation of the Dipeptide Permease Promoter (PdppA) in Group A Streptococcus

2006 ◽  
Vol 189 (4) ◽  
pp. 1407-1416 ◽  
Author(s):  
Asiya A. Gusa ◽  
Barbara J. Froehlich ◽  
Devak Desai ◽  
Virginia Stringer ◽  
June R. Scott
Keyword(s):  
Group A Streptococcus ◽  
Response Regulator ◽  
Activation Of Transcription ◽  
Genes Encoding ◽  
Group A ◽  
Transcription In Vitro ◽  
Dna Template ◽  
Regulated Promoters

ABSTRACT CovR, the two-component response regulator of Streptococcus pyogenes (group A streptococcus [GAS]) directly or indirectly represses about 15% of the genome, including genes encoding many virulence factors and itself. Transcriptome analyses also showed that some genes are activated by CovR. We asked whether the regulation by CovR of one of these genes, dppA, the first gene in an operon encoding a dipeptide permease, is direct or indirect. Direct regulation by CovR was suggested by the presence of five CovR consensus binding sequences (CBs) near the putative promoter. In this study, we identified the 5′ end of the dppA transcript synthesized in vivo and showed that the start of dppA transcription in vitro is the same. We found that CovR binds specifically to the dppA promoter region (PdppA) in vitro with an affinity similar to that at which it binds to other CovR-regulated promoters. Disruption of any of the five CBs by a substitution of GG for TT inhibited CovR binding to that site in vitro, and binding at two of the CBs appeared cooperative. In vivo, CovR activation of transcription was not affected by individual mutations of any of the four CBs that we could study. This suggests that the binding sites are redundant in vivo. In vitro, CovR did not activate transcription from PdppA in experiments using purified GAS RNA polymerase and either linear or supercoiled DNA template. Therefore, we propose that in vivo, CovR may interfere with the binding of a repressor of PdppA.

scholarly journals Serine/Threonine Protein Kinase Stk Is Required for Virulence, Stress Response, and Penicillin Tolerance in Streptococcus pyogenes

2011 ◽  
Vol 79 (10) ◽  
pp. 4201-4209 ◽  
Author(s):  
Julia Bugrysheva ◽  
Barbara J. Froehlich ◽  
Jeffrey A. Freiberg ◽  
June R. Scott
Keyword(s):  
Streptococcus Pyogenes ◽  
Fatty Acid Biosynthesis ◽  
Group A Streptococcus ◽  
Acid Biosynthesis ◽  
Regulation Of Expression ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Genes Encoding ◽  
Group A

ABSTRACTGenes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogenStreptococcus pyogenes(group A streptococcus [GAS]). We report that in GAS,stkis required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of α-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that thestkdeletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence.

scholarly journals Distinct Time-Resolved Roles for Two Catabolite-Sensing Pathways duringStreptococcus pyogenesInfection

2010 ◽  
Vol 79 (2) ◽  
pp. 812-821 ◽  
Author(s):  
Colin C. Kietzman ◽  
Michael G. Caparon
Keyword(s):  
Streptococcus Pyogenes ◽  
Virulence Genes ◽  
Group A Streptococcus ◽  
Transcriptome Profiling ◽  
Time Resolved ◽  
Group A ◽  
Global Transcriptome ◽  
Carbon Catabolite Regulation ◽  
Catabolite Regulation

ABSTRACTMany Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression inStreptococcus pyogenes(group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this responsein vitro. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA−versus LacD.1−mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection.

scholarly journals Identification and Characterization of Bicistronic speB and prsA Gene Expression in the Group A Streptococcus

2006 ◽  
Vol 188 (21) ◽  
pp. 7626-7634 ◽  
Author(s):  
Yongsheng Ma ◽  
Amy E. Bryant ◽  
Dan B. Salmi ◽  
Susan M. Hayes-Schroer ◽  
Eric McIndoo ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Genetic Regulation ◽  
Active Form ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Invasive Group ◽  
Genes Encoding ◽  
Group A ◽  
Streptococcal Pyrogenic Exotoxin B

ABSTRACT Severe, invasive group A streptococcal infections have reemerged worldwide, and extracellular toxins, including streptococcal pyrogenic exotoxin B (SpeB), have been implicated in pathogenesis. The genetic regulation of SpeB is not fully understood, and the mechanisms involved in the processing of the protoxin to its enzymatically active form have not been definitively established. The present work demonstrated that the genes encoding SpeB (speB) and a peptidyl-prolyl isomerase (prsA) constitute an operon with transcription initiated from two promoters upstream of speB. Further, the speB-prsA operon was transcribed as a bicistronic mRNA. This finding is in contrast to the generally accepted notion that speB is transcribed only as a monocistronic gene. In addition, prsA has its own promoter, and transcription from this promoter starts in early log phase, prior to the transcription of speB. Genomic disruption of prsA decreased the production of enzymatically active SpeB but not the level of the pro-SpeB zymogen. Taken together, these results demonstrate that prsA is required for production of fully mature, enzymatically active SpeB.

scholarly journals Pyogenic Streptococci – Danger of Re-Emerging Pathogens

2010 ◽  
Vol 59 (4) ◽  
pp. 219-226 ◽  
Author(s):  
IZABELA SITKIEWICZ ◽  
WALERIA HRYNIEWICZ
Keyword(s):  
Group A Streptococcus ◽  
Emerging Pathogens ◽  
Animal Pathogens ◽  
Invasive Infections ◽  
Group A ◽  
Severe Infections ◽  
Multiple Species ◽  
Streptococcus Canis ◽  
Major Surface ◽  
Human Infections

Beta-hemolytic, pyogenic streptococci are classified according to type of major surface antigen into A (Streptococcus pyogenes), B (Streptococcus agalactiae), C (multiple species including Streptococcus dysagalactiae) and G (multiple species including Streptococcus canis) Lancefield groups. Group A Streptococcus causes each year hundreds of thousands deaths globally as a result of infections and post-infectional sequelae. An increasing number of severe, invasive infections is caused by selected, specialized pathogenic clones. Within the last 50 years, an increasing number of human infections caused by groups B, C and G Streptococcus (GBS, GCS, GGS) has been observed worldwide. GBS was first identified as animal pathogen but the spectrum of diseases caused by GBS quickly shifted to human infections. Groups C and G Streptococcus are still regarded mostly as animal pathogens, however, an increased number of severe infections caused by these groups is observed. The increasing number of human infections caused worldwide by GCS/GGS can be a sign of similar development from animal to human pathogen as observed in case of GBS and this group will gain much more clinical interest in the future.The situation in Poland regarding invasive infections caused by pyogenic streptococci is underestimated.

scholarly journals Gene fitness landscape of group A streptococcus during necrotizing myositis

2018 ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
Matthew Ojeda Saavedra ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Group A Streptococcus ◽  
Insertion Site ◽  
Pcr Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Necrotizing Myositis ◽  
Genes Encoding ◽  
Isogenic Mutant Strain ◽  
Group A

ABSTRACTNecrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.

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