scholarly journals Macrophage cytokine responses to commensal Gram-positive Lactobacillus salivarius strains are TLR2-independent and Myd88-dependent

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sreeram Udayan ◽  
Ludovica F. Buttó ◽  
Valerio Rossini ◽  
Janaki Velmurugan ◽  
Maria Martinez-Lopez ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Host Cells ◽  
Lactobacillus Salivarius ◽  
Gram Positive ◽  
Cytokine Responses ◽  
Tlr2 Ligand ◽  
Different Strains ◽  
Macrophage Cytokine

AbstractThe mechanisms through which cells of the host innate immune system distinguish commensal bacteria from pathogens are currently unclear. Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) expressed by host cells which recognize microbe-associated molecular patterns (MAMPs) common to both commensal and pathogenic bacteria. Of the different TLRs, TLR2/6 recognize bacterial lipopeptides and trigger cytokines responses, especially to Gram-positive and Gram-negative pathogens. We report here that TLR2 is dispensable for triggering macrophage cytokine responses to different strains of the Gram-positive commensal bacterial species Lactobacillus salivarius. The L. salivarius UCC118 strain strongly upregulated expression of the PRRs, Mincle (Clec4e), TLR1 and TLR2 in macrophages while downregulating other TLR pathways. Cytokine responses triggered by L. salivarius UCC118 were predominantly TLR2-independent but MyD88-dependent. However, macrophage cytokine responses triggered by another Gram-positive commensal bacteria, Bifidobacterium breve UCC2003 were predominantly TLR2-dependent. Thus, we report a differential requirement for TLR2-dependency in triggering macrophage cytokine responses to different commensal Gram-positive bacteria. Furthermore, TNF-α responses to the TLR2 ligand FSL-1 and L. salivarius UCC118 were partially Mincle-dependent suggesting that PRR pathways such as Mincle contribute to the recognition of MAMPs on distinct Gram-positive commensal bacteria. Ultimately, integration of signals from these different PRR pathways and other MyD88-dependent pathways may determine immune responses to commensal bacteria at the host-microbe interface.

scholarly journals Synthesis and Antimicrobial Activity of Phosphonopeptide Derivatives Incorporating Single and Dual Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1557 ◽  
Author(s):  
Keng Tiong Ng ◽  
John D. Perry ◽  
Emma C.L. Marrs ◽  
Sylvain Orenga ◽  
Rosaleen J. Anderson ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Culture Media ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Selective Inhibitors ◽  
Selective Agents ◽  
Enzyme Substrates ◽  
Dual Inhibitors ◽  
Different Strains ◽  
Diagnostic Microbiology

In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of “suicide substrates” that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on d/l-fosfalin and β-chloro-l-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including Salmonella, Pseudomonas aeruginosa, and Listeria.

scholarly journals hfqPlays Important Roles in Virulence and Stress Adaptation in Cronobacter sakazakii ATCC 29544

2015 ◽  
Vol 83 (5) ◽  
pp. 2089-2098 ◽  
Author(s):  
Seongok Kim ◽  
Hyelyeon Hwang ◽  
Kwang-Pyo Kim ◽  
Hyunjin Yoon ◽  
Dong-Hyun Kang ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Soft Agar ◽  
Host Cells ◽  
Neonatal Meningitis ◽  
Animal Cells ◽  
Content Type ◽  
Flagellar Biosynthesis

Cronobacterspp. are opportunistic pathogens that cause neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated withCronobacterinfection, the mechanisms of pathogenesis are still being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq inC. sakazakiivirulence. In the absence ofhfq,C. sakazakiiwas highly attenuated in disseminationin vivo, showed defects in invasion (3-fold) into animal cells and survival (103-fold) within host cells, and exhibited low resistance to hydrogen peroxide (102-fold). Remarkably, the loss ofhfqled to hypermotility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyperflagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagellar biosynthesis in a strain lackinghfq. Together, these data strongly suggest thathfqplays important roles in the virulence ofC. sakazakiiby participating in the regulation of multiple genes.

scholarly journals Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

2017 ◽  
Vol 24 (10) ◽  
Author(s):  
Giulia Malachin ◽  
Elisa Lubian ◽  
Fabrizio Mancin ◽  
Emanuele Papini ◽  
Regina Tavano
Keyword(s):  
Dendritic Cells ◽  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Content Type ◽  
E Coli ◽  
Synergistic Induction ◽  
Ifn Γ

ABSTRACT Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (Escherichia coli, Staphylococcus epidermidis) or pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) in the presence of amorphous silica nanoparticles (SiO2 NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. E. coli and S. epidermidis EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1β (IL-1β), IL-12, IL-10, and IL-6, while E. coli and S. epidermidis EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, and IL-5. On the contrary, S. aureus and P. aeruginosa EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO2 NP doses. DCs consistently supported the proliferation and differentiation of CD4+ and CD8+ T cells secreting IFN-γ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1β was prevalently mediated by proteins in the case of E. coli EMs and by nonproteins in the case of S. epidermidis EMs. A bacterial costimulus did not act on DCs after adsorption on SiO2 NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.

scholarly journals Anthra[1,2-d][1,2,3]triazine-4,7,12(3H)-triones as a New Class of Antistaphylococcal Agents: Synthesis and Biological Evaluation

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4581
Author(s):  
Viktor Zvarych ◽  
Maryna Stasevych ◽  
Volodymyr Novikov ◽  
Eduard Rusanov ◽  
Mykhailo Vovk ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Modern Medicine ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Mrsa Strains ◽  
Time Kill

The development and spread of resistance of human pathogenic bacteria to the action of commonly used antibacterial drugs is one of the key problems in modern medicine. One of the especially dangerous and easily developing antibiotic resistant bacterial species is Staphylococcus aureus. Anthra[1,2-d][1,2,3]triazine-4,7,12(3H)-triones 22–38 have been developed as novel effective antistaphylococcal agents. These compounds have been obtained by sequential conversion of 1-amino-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid (1) and 1-amino-4-bromo-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid (2) into the corresponding amides 5–21, followed by subsequent endo-cyclization under the influence of sodium nitrite in acetic acid. Evaluation of the antimicrobial activity of the synthesized compounds against selected species of Gram-positive and Gram-negative bacteria as well as pathogenic yeasts of the Candida genus has been carried out by the serial dilution method. It has been established that anthra[1,2-d][1,2,3]triazine-4,7,12(3H)-triones exhibit selective antibacterial activity against Gram-positive bacteria. Eight, six and seven, out of seventeen compounds tested, effectively inhibited the growth of S. aureus ATCC 25923, S. aureus ATCC 29213 and S. epidermidis ATCC12228, respectively, at a concentration equal to 1 µg/mL or lower. The high antistaphylococcal potential of the most active compounds has been also confirmed against clinical isolates of S. aureus, including the MRSA strains. However, bacteria of the Staphylococcus genus have demonstrated apparent resistance to the novel compounds when grown as a biofilm. None of the four selected compounds 3234 and 36 at a concentration of 64 µg/mL (128 or 256 × MIC—against planktonic cells) has caused any decrease in the metabolic activity of the staphylococcal cells forming the biofilm. The kinetic time–kill assay revealed some important differences in the activity of these substances. Compound 33 is bacteriostatic, while the other three demonstrate bactericidal activity.

scholarly journals Antimicrobial susceptibility of bacteria isolated from the infected wounds of patients with lymphoedema in East Wollega, Ethiopia

2020 ◽  
Vol 114 (12) ◽  
pp. 962-973
Author(s):  
Dereje Nigussie ◽  
Eyasu Makonnen ◽  
Belete Adefris Legesse ◽  
Abebaw Fekadu ◽  
Gail Davey
Keyword(s):  
Wound Infection ◽  
Antimicrobial Susceptibility ◽  
Pathogenic Bacteria ◽  
Detection System ◽  
Multiple Drug Resistance ◽  
Bacterial Species ◽  
Multiple Drug ◽  
Gram Positive ◽  
Gram Negative ◽  
Culture Positive

Abstract Background Lymphoedema is caused by dysfunction of the lymphatic system resulting in accumulation of high-protein content fluid in the interstitial space. To date, the bacteria associated with wound infections of patients with lower limb lymphoedema in Ethiopia have not been studied. This study identified pathogenic bacteria involved in wound infection and assessed antimicrobial susceptibility patterns in patients with lymphoedema in Ethiopia. Methods Swab samples were collected from the wounds of patients with lymphoedema and cultured using standard microbiological techniques. Micro-organisms were identified by colony morphology followed by identification and antimicrobial susceptibility testing using the automated VITEK 2 COMPACT Microbial Detection System. Results Swabs were collected from 103 patients and 84 were culture positive: 44 (52.4%) culture-positive samples showed polymicrobial growth and 40 (47.6%) grew single bacterial isolates. In total, 134 isolates were obtained, of which 26 gram-negative and 12 gram-positive bacterial species were identified. A total of 28/63 (44.4%) gram-negative isolates and 3/57 (5.3%) gram-positive isolates were multiple drug resistant. There was no resistance to ciprofloxacin, moxifloxacin or gentamycin among gram-negative or gram-positive bacteria. Conclusion In this study, many infections were polymicrobial and showed multiple drug resistance. Fluoroquinolones and gentamycin, however, seemed to be effective against bacterial wound infection in this setting.

scholarly journals Gastrointestinal Inflammation and the Gut Microbiome: An Evolving Conceptual Framework with Implications for Diagnosis and Therapy in Inflammatory Bowel Disorders

2020 ◽  
pp. 42-50
Author(s):  
Oliver Grundmann
Keyword(s):  
Inflammatory Bowel Disease ◽  
Systemic Inflammation ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Low Grade ◽  
Environmental Toxicants ◽  
Inflammatory Bowel

The human gut microbiome has garnered much attention over the past two decades with important discoveries linking it to human health and disease. The commensal bacterial flora evolves due to the influence of a number of factors including diet, pathogen exposure, environmental toxicants, disease states, and a challenged microenvironment that requires balancing with the host itself. However, the composition of bacterial species can impact and contribute to the development of local and systemic inflammation. Among the factors attributed to intestinal inflammation are dysbiosis caused by pathogenic bacteria, following decreased host immunity or loss of intestinal barrier function. Dysbiosis can also be triggered by antibiotic therapy or the use of other medications that allow for colonisation of pathogenic bacteria, such as proton pump inhibitors. The imbalance with commensal bacteria leads to the generation of proinflammatory mediators and a reduction of host immune defences, due to a lack of short-chain fatty acid generation needed for energy production to maintain barrier and immune function. The initially localised inflammation results in further dysbiosis as former commensal bacteria are able to breach the barrier and cause systemic immune responses. Low-grade systemic inflammation is a hallmark of inflammatory bowel disease. Because a specific dysbiosis is common in patients with inflammatory bowel disease, it can serve as an early diagnostic marker in its development. Furthermore, faecal microbiome transplants have shown promising benefits in patients with ulcerative colitis and Crohn’s disease.

scholarly journals The Lignan-containing Extract of Schisandra chinensis Berries Inhibits the Growth of Chlamydia pneumoniae

2015 ◽  
Vol 10 (6) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Elina Hakala ◽  
Leena L. Hanski ◽  
Teijo Yrjönen ◽  
Heikki J. Vuorela ◽  
Pia M. Vuorela
Keyword(s):  
Chlamydia Pneumoniae ◽  
Bacterial Species ◽  
Host Cells ◽  
Schisandrin B ◽  
Respiratory Pathogens ◽  
Dependent Manner ◽  
Schisandra Chinensis ◽  
Pure Compound ◽  
Different Strains ◽  
Dose Dependent

The purpose of this study was to investigate the effect and selectivity of an extract of Schisandra chinensis berries against Chlamydia pneumoniae and C. trachomatis. Among the ethnopharmacological uses of the extract from Schisandrae fructus are cough and pneumonia. Therefore we focused on respiratory pathogens. The extract completely inhibited the growth of C. pneumoniae strain CV6 at 250 μg/mL concentration. The inhibition of C. pneumoniae and C. trachomatis growth was dose dependent and established with three different strains. The extract inhibited C. pneumoniae production of infectious progeny in a dose dependent manner. Chlamydia selectivity was elucidated with growth inhibition measurements of three other respiratory bacterial species. A pure compound found in Schisandra chinensis berries, schisandrin B at 20.0 μg/mL concentration inhibited the growth of both C. pneumoniae and C. trachomatis. The extract was found to be non-toxic to the human host cells. These findings highlight the potential of the extract from Schisandra chinensis berries as a source for antichlamydial compounds.

scholarly journals Novel Broad-Spectrum Bis-(Imidazolinylindole) Derivatives with Potent Antibacterial Activities against Antibiotic-Resistant Strains

2009 ◽  
Vol 53 (10) ◽  
pp. 4283-4291 ◽  
Author(s):  
Rekha G. Panchal ◽  
Ricky L. Ulrich ◽  
Douglas Lane ◽  
Michelle M. Butler ◽  
Chad Houseweart ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
In Vivo Studies ◽  
Structural Variations ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Resistant Strains

ABSTRACT Given the limited number of structural classes of clinically available antimicrobial drugs, the discovery of antibacterials with novel chemical scaffolds is an important strategy in the development of effective therapeutics for both naturally occurring and engineered resistant strains of pathogenic bacteria. In this study, several diarylamidine derivatives were evaluated for their ability to protect macrophages from cell death following infection with Bacillus anthracis, a gram-positive spore-forming bacterium. Four bis-(imidazolinylindole) compounds were identified with potent antibacterial activity as measured by the protection of macrophages and by the inhibition of bacterial growth in vitro. These compounds were effective against a broad range of gram-positive and gram-negative bacterial species, including several antibiotic-resistant strains. Minor structural variations among the four compounds correlated with differences in their effects on bacterial macromolecular synthesis and mechanisms of resistance. In vivo studies revealed protection by two of the compounds of mice lethally infected with B. anthracis, Staphylococcus aureus, or Yersinia pestis. Taken together, these results indicate that the bis-(imidazolinylindole) compounds represent a new chemotype for the development of therapeutics for both gram-positive and gram-negative bacterial species as well as against antibiotic-resistant infections.

scholarly journals Escherichia coli Shiga Toxins and Gut Microbiota Interactions

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 416
Author(s):  
Kyung-Soo Lee ◽  
Yu-Jin Jeong ◽  
Moo-Seung Lee
Keyword(s):  
Escherichia Coli ◽  
Bacterial Communities ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Shigella Dysenteriae ◽  
Host Cells ◽  
Severe Illness ◽  
Shiga Toxins ◽  
Serotype 1 ◽  
Lethal Complications

Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species of bacteria produce Shiga toxins (Stxs), a phage-encoded exotoxin inhibiting protein synthesis in host cells that are primarily responsible for bacterial virulence. Although most studies have focused on the pathogenic roles of Stxs as harmful substances capable of inducing cell death and as proinflammatory factors that sensitize the host target organs to damage, less is known about the interface between the commensalism of bacterial communities and the pathogenicity of the toxins. The gut contains more species of bacteria than any other organ, providing pathogenic bacteria that colonize the gut with a greater number of opportunities to encounter other bacterial species. Notably, the presence in the intestines of pathogenic EHEC producing Stxs associated with severe illness may have compounding effects on the diversity of the indigenous bacteria and bacterial communities in the gut. The present review focuses on studies describing the roles of Stxs in the complex interactions between pathogenic Shiga toxin-producing E. coli, the resident microbiome, and host tissues. The determination of these interactions may provide insights into the unresolved issues regarding these pathogens.

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