scholarly journals The Relevance of IL-1-Signaling in the Protection against Gram-Positive Bacteria

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 132
Author(s):  
Angelina Midiri ◽  
Giuseppe Mancuso ◽  
Concetta Beninati ◽  
Elisabetta Gerace ◽  
Carmelo Biondo

Previous studies performed using a model of group B streptococcus (GBS)-induced peritoneal inflammation indicate that the interleukin-1 receptor (IL-1R) family plays an important role in the innate host defense against this encapsulated Gram-positive bacteria. Since the role of IL-1-dependent signaling in peritoneal infections induced by other Gram-positive bacteria is unknown, in the present study we sought to investigate the contribution of IL-1R signaling in host defenses against Streptococcus pyogenes (group A streptococcus or GAS) or Staphylococcus aureus, two frequent and global human Gram-positive extracellular pathogens. We analyzed here the outcome of GAS or S. aureus infection in IL-1R-deficient mice. After inoculated intraperitoneal (i.p.) inoculation with group A Streptococcus or S. aureus, all the wild-type (WT) control mice survived the challenge, while, respectively, 63% or 50% of IL-1-defective mice died. Lethality was due to the ability of both bacterial species to replicate and disseminate to the target organs of IL-1R-deficient mice. Moreover, the experimental results indicate that IL-1 signaling promotes the production of leukocyte attractant chemokines CXCL-1 and CXCL-2 and recruitment of neutrophils to bacterial infection sites. Accordingly, the reduced neutrophil recruitment in IL-1R-deficient mice was linked with decreased production of neutrophil chemokines. Collectively, our findings indicate that IL-1 signaling, as previously showed in host defense against GBS, plays a fundamental role also in controlling the progression and outcome of GAS or S. aureus disease.

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Ulrike Resch ◽  
James Anthony Tsatsaronis ◽  
Anaïs Le Rhun ◽  
Gerald Stübiger ◽  
Manfred Rohde ◽  
...  

ABSTRACT Export of macromolecules via extracellular membrane-derived vesicles (MVs) plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS), the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response. IMPORTANCE Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 500,000 deaths annually. Establishment of GAS infection is dependent on a suite of proteins exported via the general secretory pathway. Here, we show that GAS naturally produces extracellular vesicles with a unique lipid composition that are laden with proteins and RNAs. Interestingly, both virulence-associated proteins and RNA species were found to be differentially abundant in vesicles relative to the bacteria. Furthermore, we show that genetic disruption of the virulence-associated two-component regulator CovRS leads to an increase in vesicle production. This study comprehensively describes the protein, RNA, and lipid composition of GAS-secreted MVs and alludes to a regulatory system impacting this process.


PEDIATRICS ◽  
1993 ◽  
Vol 91 (1) ◽  
pp. 148-149
Author(s):  
JOHN W. LARSEN ◽  
SHARON L. DOOLEY

Group B Streptococcus (GBS) was first identified as a cause of puerperal sepsis during the late 1930s. However, concern regarding GBS was diminished in part by the greater pathogenicity of the group A Streptococcus, which was described in the same studies. Clinical research regarding GBS infections resumed during the 1960s. Data regarding the perinatal transmission of GBS have now accumulated to an extent that education of all obstetric and pediatric care providers is imperative. During the past 2 years, committees of both the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) have considered the issues of perinatal transmission of GBS. Each group had input from the other by a series of meetings and document exchanges.


2009 ◽  
Vol 191 (7) ◽  
pp. 2257-2265 ◽  
Author(s):  
Mark R. Davies ◽  
Josephine Shera ◽  
Gary H. Van Domselaar ◽  
Kadaba S. Sriprakash ◽  
David J. McMillan

ABSTRACT Lateral gene transfer is a significant contributor to the ongoing evolution of many bacterial pathogens, including β-hemolytic streptococci. Here we provide the first characterization of a novel integrative conjugative element (ICE), ICESde3396, from Streptococcus dysgalactiae subsp. equisimilis (group G streptococcus [GGS]), a bacterium commonly found in the throat and skin of humans. ICESde3396 is 64 kb in size and encodes 66 putative open reading frames. ICESde3396 shares 38 open reading frames with a putative ICE from Streptococcus agalactiae (group B streptococcus [GBS]), ICESa2603. In addition to genes involves in conjugal processes, ICESde3396 also carries genes predicted to be involved in virulence and resistance to various metals. A major feature of ICESde3396 differentiating it from ICESa2603 is the presence of an 18-kb internal recombinogenic region containing four unique gene clusters, which appear to have been acquired from streptococcal and nonstreptococcal bacterial species. The four clusters include two cadmium resistance operons, an arsenic resistance operon, and genes with orthologues in a group A streptococcus (GAS) prophage. Streptococci that naturally harbor ICESde3396 have increased resistance to cadmium and arsenate, indicating the functionality of genes present in the 18-kb recombinogenic region. By marking ICESde3396 with a kanamycin resistance gene, we demonstrate that the ICE is transferable to other GGS isolates as well as GBS and GAS. To investigate the presence of the ICE in clinical streptococcal isolates, we screened 69 isolates (30 GGS, 19 GBS, and 20 GAS isolates) for the presence of three separate regions of ICESde3396. Eleven isolates possessed all three regions, suggesting they harbored ICESde3396-like elements. Another four isolates possessed ICESa2603-like elements. We propose that ICESde3396 is a mobile genetic element that is capable of acquiring DNA from multiple bacterial sources and is a vehicle for dissemination of this DNA through the wider β-hemolytic streptococcal population.


2021 ◽  
Vol 47 (11) ◽  
pp. 491-499
Author(s):  
Grace Huang ◽  
Irene Martin ◽  
Raymond S Tsang ◽  
Walter H Demczuk ◽  
Gregory J Tyrrell ◽  
...  

Background: The International Circumpolar Surveillance (ICS) program conducts surveillance on five invasive bacterial diseases: pneumococcal disease (IPD), group A streptococcus (iGAS), Haemophilus influenzae (Hi), meningococcal disease (IMD) and group B streptococcus (GBS). Invasive bacterial diseases have a higher burden of disease in northern populations than the rest of Canada. Methods: To describe the epidemiology of invasive bacterial diseases in northern Canada from 1999 to 2018, data for IPD, iGAS, Hi, IMD and GBS were extracted from the ICS program and the Canadian Notifiable Diseases Surveillance System (CNDSS) and analyzed. Results: The annualized incidence rates for IPD, iGAS, Hi, GBS and IMD were 23.3, 10.5, 8.9, 1.9 and 1.1 per 100,000 population, respectively. The incidence of IPD, iGAS and Hi serotype b were 2.8, 3.2 and 8.8 times higher, respectively, in northern Canada than in the rest of Canada. Rates of disease decreased statistically significantly for IPD (β=−0.02) and increased statistically for iGAS (β=0.08) and Hi serotype a (β=0.04) during the study period. In Northern Canada, the annualized incidence rates for IPD, iGAS and Hi were statistically higher for Indigenous residents than for non-Indigenous residents. The highest incidence rates were among the very young and older age groups. Conclusion: Invasive bacterial diseases represent a high burden of disease in Canada’s northern populations. Indigenous peoples, children and seniors are particularly at risk.


1999 ◽  
Vol 43 (4) ◽  
pp. 930-936 ◽  
Author(s):  
Kumthorn Malathum ◽  
Teresa M. Coque ◽  
Kavindra V. Singh ◽  
Barbara E. Murray

ABSTRACT The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus,Enterococcus faecalis, Enterococcus faecium,Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (Ems), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 μg/ml; range, 0.03 to 0.06 μg/ml; MIC50 [erythromycin], 0.25 μg/ml; range, 0.25 to 0.5 μg/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of >64 μg/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC ≤ 0.5 μg/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 μg/ml were 0.015 μg/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 μg/ml showed HMR 3647 MICs in the range of 0.03 to 16 μg/ml and HMR 3004 MICs in the range of 0.03 to 64 μg/ml. In the group of E. faecium strains for which MICs of erythromycin were ≥512 μg/ml, MICs of both ketolides were in the range of 1 to 64 μg/ml, with almost all isolates showing ketolide MICs of ≤16 μg/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci,S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.


Sexual Health ◽  
2006 ◽  
Vol 3 (3) ◽  
pp. 187 ◽  
Author(s):  
Susan Bray ◽  
Jane Morgan

Two cases of group A streptococcus (GAS) causing vulvovaginitis in premenopausal adults are described. A review of the literature of genital GAS is made, as this is an uncommon cause of vulvovaginitis in premenopausal adults. Contrasts are made between anogenital carriage of GAS and group B streptococcus (GBS) to highlight the differences in anogenital carriage between these two organisms.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S593-S593
Author(s):  
Emily Mosites ◽  
Tammy Zulz ◽  
Dana Bruden ◽  
Leisha Nolen ◽  
Anna Frick ◽  
...  

Abstract Background People experiencing homelessness (PEH) have an increased risk of infectious disease. However, for many infections, this increased risk has not been clearly quantified. For example, the risk of invasive streptococcal infection has not been established among PEH in the United States. Methods We compared the incidence of detected cases of invasive group A Streptococcus (GAS) infection, group B Streptococcus (GBS) infection, and Streptococcus pneumoniae (pneumococcal) infection among adult PEH to that in the general adult population in Anchorage, Alaska from 2005 through 2015 using data from the CDC Arctic Investigations Program surveillance system, the US census, and the Anchorage Point in Time count (PIT [a yearly census of PEH]). Results During 2005–2015, the PIT counted a mean number of 970 adults (minimum 795, maximum 1486) in Anchorage who were homeless, which accounted for 0.4% of the total population. Compared with the general population, PEH were 53 times as likely to have invasive GAS infection (95% CI 47–61), 7 times as likely to have invasive GBS infection (95% CI 6, 8), and 36 times as likely to have invasive pneumococcal infection (95% CI 33, 40). Of all invasive GAS cases in Anchorage over the time period, 19% occurred within the homeless population, while 3% of invasive GBS cases and 14% of invasive pneumococcal cases were within the homeless population. Additionally, the predominant subtypes of GAS and pneumococcus differed among PEH compared with the general population. Conclusion A disproportionate burden of invasive streptococcal disease in Anchorage was detected among PEH, indicating a need for further focus on this high-risk group. Disclosures All authors: No reported disclosures.


1959 ◽  
Vol 109 (4) ◽  
pp. 361-378 ◽  
Author(s):  
Maclyn McCarty

A bacterial substance has been described which gives a precipitin reaction with certain antisera to Group A streptococci. The precipitating antigen is present in various Gram-positive bacteria, including most hemolytic streptococci, staphylococci, and aerobic sporulating bacilli. It is not present in any of the Gram-negative species examined or in pneumococci, clostridia, or corynebacteria. Analysis of purified preparations obtained from Group A streptococci indicates that the antigen is a simple polymer of glycerophosphate. The identification has been confirmed by immunochemical studies, including precipitin tests and specific inhibition with synthetic polyglycerophosphates. In addition, the infrared spectra of bacterial and synthetic polyglycerophosphate are shown to be closely similar. Immunochemical analysis suggests that the amount of polyglycerophosphate present in Group A streptococci and staphylococci is approximately 1 per cent of the dry weight of the cells. The cellular localization and function of the polyglycerophosphate have not been established.


2018 ◽  
Author(s):  
Vincent P. van Hensbergen ◽  
Elin Movert ◽  
Vincent de Maat ◽  
Christian Lüchtenborg ◽  
Yoann Le Breton ◽  
...  

AbstractHuman Group IIA secreted phospholipase A2(hGIIA) is an acute phase protein with bactericidal activity against Gram-positive bacteria. Infection models in hGIIA transgenic mice have suggested the importance of hGIIA as an innate defense mechanism against the human pathogens Group AStreptococcus(GAS) and Group BStreptococcus(GBS). Compared to other Gram-positive bacteria, GAS is remarkably resistant to hGIIA activity. To identify GAS resistance mechanisms, we exposed a highly saturated GAS M1 transposon library to recombinant human hGIIA and compared relative mutant abundance with library input through transposon-sequencing (Tn-seq). Based on transposon prevalence in the output library, we identified nine genes, includingdltAandlytR,conferring increased hGIIA susceptibility. In addition, seven genes conferred increased hGIIA resistance, which included two genes,gacHandgacIthat are located within the Group A Carbohydrate (GAC) gene cluster. Using GAS 5448 wild-type and the isogenicgacImutant and gacI-complemented strains, we demonstrate that loss of the GACN-acetylglucosamine (GlcNAc) side chain in theΔgacImutant increases hGIIA resistance approximately 10-fold, a phenotype that is conserved across different GAS serotypes. Increased resistance is associated with delayed penetration of hGIIA through the cell wall. Correspondingly, loss of the Lancefield Group B Carbohydrate (GBC) rendered GBS significantly more resistant to hGIIA-mediated killing. This suggests that the streptococcal Lancefield antigens, which are critical determinants for streptococcal physiology and virulence, are required for the human bactericidal enzyme hGIIA to exert its bactericidal function.Author summaryThe human immune system is capable of killing invading bacteria by secreting antimicrobial proteins. Cationic human Group IIA secreted phospholipase A2(hGIIA) is especially effective against Gram-positive bacteria by degrading the bacterial membrane. HGIIA requires binding to negatively charged surface structures before it can penetrate through the thick peptidoglycan layer and reach the target phospholipid membrane. HGIIA is constitutively expressed at high concentrations at sites of possible bacterial entry, e.g. in tears, skin and small intestine. In serum, normal concentrations are low but can increase up to 1,000-fold upon inflammation or infection.In vitro,ex vivoandin vivoexperiments suggest an important role for hGIIA in defense against two human pathogens, Group A and Group BStreptococcus(GAS, GBS). We demonstrate that the Lancefield cell wall polysaccharides that are expressed by these bacteria, the Group A Carbohydrate (GAC) for GAS and the Group B Carbohydrate (GBC) for GBS, are required for optimal hGIIA bactericidal efficacy by facilitating penetration through the peptidoglycan layer. Given the increased hGIIA resistance of antigen-modified or antigen-deficient streptococci, it will be of interest to determine potential regulatory mechanisms regarding expression of streptococcal Lancefield polysaccharides.


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