scholarly journals Kingella kingaeSurface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Vanessa L. Muñoz ◽  
Eric A. Porsch ◽  
Joseph W. St. Geme
Keyword(s):  
Young Children ◽  
Antimicrobial Peptides ◽  
Bacterial Pathogens ◽  
Human Neutrophils ◽  
Kingella Kingae ◽  
Gram Negative ◽  
Content Type ◽  
Polysaccharide Capsule ◽  
Potential Applicability ◽  
Bacterial Exopolysaccharide

ABSTRACTBacterial pathogens have evolved strategies that enable them to evade neutrophil-mediated killing. The Gram-negative coccobacillusKingella kingaeis an emerging pediatric pathogen and is increasingly recognized as a common etiological agent of osteoarticular infections and bacteremia in young children.K. kingaeproduces a polysaccharide capsule and an exopolysaccharide, both of which are important for protection against complement-mediated lysis and are required for full virulence in an infant rat model of infection. In this study, we examined the role of theK. kingaepolysaccharide capsule and exopolysaccharide in protection against neutrophil killing. In experiments with primary human neutrophils, we found that the capsule interfered with the neutrophil oxidative burst response and prevented neutrophil binding ofK. kingaebut had no effect on neutrophil internalization ofK. kingae. In contrast, the exopolysaccharide resisted the bactericidal effects of antimicrobial peptides and efficiently blocked neutrophil phagocytosis ofK. kingae. This work demonstrates that theK. kingaepolysaccharide capsule and exopolysaccharide promote evasion of neutrophil-mediated killing through distinct yet complementary mechanisms, providing additional support for theK. kingaesurface polysaccharides as potential vaccine antigens. In addition, these studies highlight a novel interplay between a bacterial capsule and a bacterial exopolysaccharide and reveal new properties for a bacterial exopolysaccharide, with potential applicability to other bacterial pathogens.IMPORTANCEKingella kingaeis a Gram-negative commensal in the oropharynx and represents a leading cause of joint and bone infections in young children. The mechanisms by whichK. kingaeevades host innate immunity during pathogenesis of disease remain poorly understood. In this study, we established that theK. kingaepolysaccharide capsule and exopolysaccharide function independently to protectK. kingaeagainst reactive oxygen species (ROS) production, neutrophil phagocytosis, and antimicrobial peptides. These results demonstrate the intricacies ofK. kingaeinnate immune evasion and provide valuable information that may facilitate development of a polysaccharide-based vaccine againstK. kingae.

scholarly journals The Type a and Type b Polysaccharide Capsules Predominate in an International Collection of Invasive Kingella kingae Isolates

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Eric A. Porsch ◽  
Kimberly F. Starr ◽  
Pablo Yagupsky ◽  
Joseph W. St. Geme
Keyword(s):  
Young Children ◽  
Septic Arthritis ◽  
Type A ◽  
Global Distribution ◽  
Type B ◽  
Kingella Kingae ◽  
Content Type ◽  
Polysaccharide Capsule ◽  
Polysaccharide Capsules ◽  
Specific Virulence

ABSTRACT Kingella kingae has emerged as a significant cause of septic arthritis, osteomyelitis, and bacteremia in young children. A recent study examining a diverse collection of K. kingae isolates from Israel revealed four different polysaccharide capsule types in this species, designated types a to d. To determine the global distribution of K. kingae capsule types, we assembled and capsule typed an international collection of K. kingae isolates. The findings reported here show that the type a and type b capsules represent >95% of the invasive isolates, similar to the Israeli isolate collection, suggesting that a polysaccharide-based vaccine targeting these two capsules could be an attractive approach to prevent K. kingae disease. Kingella kingae is an encapsulated Gram-negative bacterium and an important etiology of osteoarticular infections in young children. A recent study examining a diverse collection of carrier and invasive K. kingae isolates from Israel revealed four distinct polysaccharide capsule types. In this study, to obtain a global view of K. kingae capsule type diversity, we examined an international collection of isolates using a multiplex PCR approach. The collection contained all four previously identified capsule types and no new capsule types. Over 95% of invasive isolates in the collection were type a or type b, similar to the findings in Israel. These results suggest that the type a and type b polysaccharide capsules may have enhanced pathogenic properties or may mark clonal groups of strains with specific virulence genes. In addition, they raise the possibility that a vaccine containing the type a and type b capsules might be an effective approach to preventing K. kingae disease. IMPORTANCE Kingella kingae has emerged as a significant cause of septic arthritis, osteomyelitis, and bacteremia in young children. A recent study examining a diverse collection of K. kingae isolates from Israel revealed four different polysaccharide capsule types in this species, designated types a to d. To determine the global distribution of K. kingae capsule types, we assembled and capsule typed an international collection of K. kingae isolates. The findings reported here show that the type a and type b capsules represent >95% of the invasive isolates, similar to the Israeli isolate collection, suggesting that a polysaccharide-based vaccine targeting these two capsules could be an attractive approach to prevent K. kingae disease.

scholarly journals A Quorum Quenching Bacterial Isolate Contains Multiple Substrate-Inducible Genes Conferring Degradation of Diffusible Signal Factor

2020 ◽  
Vol 86 (7) ◽  
Author(s):  
Huishan Wang ◽  
Lisheng Liao ◽  
Shaohua Chen ◽  
Lian-Hui Zhang
Keyword(s):  
Molecular Basis ◽  
Bacterial Isolate ◽  
Bacterial Pathogens ◽  
Quorum Quenching ◽  
Gram Negative ◽  
Content Type ◽  
Signal Degradation ◽  
Highly Active ◽  
Diffusible Signal Factor ◽  
Degradation Activity

ABSTRACT Quorum quenching, which disrupts quorum sensing (QS) by either degradation of QS signals or interference of signal generation or perception, is a promising strategy for the prevention and control of QS-mediated bacterial infections. Diffusible signal factor (DSF) is widely conserved in many Gram-negative bacterial pathogens. In this study, we developed an efficient method for screening of highly active DSF degradation microorganisms. Among them, Pseudomonas sp. strain HS-18 showed a superior DSF degradation activity. Bioinformatics and genetic analyses showed that at least 4 genes, designated digA to digD, encoding fatty acyl coenzyme A ligase homologues, are responsible for DSF signal degradation. Interestingly, all 4 dig genes were induced by exogenous DSF, with digA being the most significantly induced. Expression of the dig genes in Xanthomonas campestris pv. campestris markedly reduced the accumulation of endogenous DSF, decreased production of virulence factors, and attenuated bacterial virulence on host plants. Similarly, application of strain HS-18 as a biocontrol agent could substantially reduce the disease severity caused by X. campestris pv. campestris. These results unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful genes and biocontrol agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens. IMPORTANCE Diffusible signal factor (DSF) represents a family of widely conserved quorum sensing signals involved in the regulation of virulence factor production in many Gram-negative bacterial pathogens. In this study, we developed a novel and efficient method for screening highly active DSF degradation microorganisms. With this method, we identified a bacterial isolate, Pseudomonas sp. strain HS-18, with a superb DSF degradation activity. We further found that strain HS-18 contains 4 genes responsible for DSF signal degradation, and significantly, these were induced by exogenous DSF molecules. These findings unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful methods, genes, and agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens.

scholarly journals In VitroActivity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Andrew Walkty ◽  
James A. Karlowsky ◽  
Melanie R. Baxter ◽  
Heather J. Adam ◽  
George G. Zhanel
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTThe Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate thein vitroactivities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potentin vitroactivity againstEnterobacteriaceae(MIC90≤ 1 µg/ml for all species tested exceptProteus mirabilisandMorganella morganii), including aminoglycoside-nonsusceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates ofStaphylococcus aureus.

scholarly journals First Identification of a Chromosomally Located Penicillinase Gene in Kingella kingae Species Isolated in Continental Europe

2014 ◽  
Vol 58 (10) ◽  
pp. 6258-6259 ◽  
Author(s):  
Romain Basmaci ◽  
Philippe Bidet ◽  
Béatrice Berçot ◽  
Christelle Jost ◽  
Thérésa Kwon ◽  
...  
Keyword(s):  
Young Children ◽  
Chromosomal Location ◽  
The Novel ◽  
Kingella Kingae ◽  
Content Type ◽  
Osteoarticular Infections ◽  
High Prevalence ◽  
First Time

ABSTRACTKingella kingaeis the major pathogen causing osteoarticular infections (OAI) in young children in numerous countries. Plasmid-borne TEM-1 penicillinase production has been sporadically detected in a few countries but not in continental Europe, despite a high prevalence ofK. kingaeinfections. We describe here for the first time aK. kingaeβ-lactamase-producing strain in continental Europe and demonstrate the novel chromosomal location of theblaTEM-1gene inK. kingaespecies.

scholarly journals In Vitro and In Vivo Profiles of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens

2011 ◽  
Vol 55 (6) ◽  
pp. 2860-2871 ◽  
Author(s):  
Michael J. Pucci ◽  
Steven D. Podos ◽  
Jane A. Thanassi ◽  
Melissa J. Leggio ◽  
Barton J. Bradbury ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Dna Replication ◽  
Bacterial Pathogens ◽  
Biological Data ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Good Antibacterial Activity

ABSTRACTACH-702, a novel isothiazoloquinolone (ITQ), was assessed for antibacterial activity against a panel of Gram-positive and Gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant Gram-positive strains, including methicillin-resistantStaphylococcus aureus(MRSA). For Gram-negative bacteria, ACH-702 showed exceptional potency againstHaemophilus influenzae,Moraxella catarrhalis, and aNeisseriasp. but was less active against members of theEnterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well asLegionella pneumophilaandMycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays, and postantibiotic effects (PAEs) of >1 h were evident with both laboratory and clinical strains of staphylococci at 10× MIC and similar in most cases to those observed for moxifloxacin at the same MIC multiple.In vivoefficacy was demonstrated againstS. aureuswith murine sepsis and thigh infection models, with decreases in the number of CFU/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci, and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism of action include the following: low MIC values (≤0.25 μg/ml) against staphylococcal strains with single mutations in bothgyrAandgrlA(parC), retention of good antibacterial activity (MICs of ≤0.5 μg/ml) against staphylococcal strains with two mutations in bothgyrAandgrlA, and low frequencies for the selection of higher-level resistance (<10−10). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates.

scholarly journals Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

2016 ◽  
Vol 82 (21) ◽  
pp. 6423-6430 ◽  
Author(s):  
Caroline Pandin ◽  
Martine Caroff ◽  
Guy Condemine
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Soft Rot ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Dickeya Dadantii ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
New Genes

ABSTRACTModification of teichoic acid through the incorporation ofd-alanine confers resistance in Gram-positive bacteria to antimicrobial peptides (AMPs). This process involves the products of thedltXABCDgenes. These genes are widespread in Gram-positive bacteria, and they are also found in a few Gram-negative bacteria. Notably, these genes are present in all soft-rot enterobacteria (PectobacteriumandDickeya) whosedltDXBACoperons have been sequenced. We studied the function and regulation of these genes inDickeya dadantii.dltBexpression was induced in the presence of the AMP polymyxin. It was not regulated by PhoP, which controls the expression of some genes involved in AMP resistance, but was regulated by ArcA, which has been identified as an activator of genes involved in AMP resistance. However,arcAwas not the regulator responsible for polymyxin induction of these genes in this bacterium, which underlines the complexity of the mechanisms controlling AMP resistance inD. dadantii. Two other genes involved in resistance to AMPs have also been characterized,phoSandphoH.dltB,phoS,phoH, andarcAbut notdltDmutants were more sensitive to polymyxin than the wild-type strain. Decreased fitness of thedltB,phoS, andphoHmutants in chicory leaves indicates that their products are important for resistance to plant AMPs.IMPORTANCEGram-negative bacteria can modify their lipopolysaccharides (LPSs) to resist antimicrobial peptides (AMPs). Soft-rot enterobacteria (DickeyaandPectobacteriumspp.) possess homologues of thedltgenes in their genomes which, in Gram-positive bacteria, are involved in resistance to AMPs. In this study, we show that these genes confer resistance to AMPs, probably by modifying LPSs, and that they are required for the fitness of the bacteria during plant infection. Two other new genes involved in resistance were also analyzed. These results show that bacterial resistance to AMPs can occur in bacteria through many different mechanisms that need to be characterized.

scholarly journals Genome Analysis of Kingella kingae Strain KWG1 Reveals How a β-Lactamase Gene Inserted in the Chromosome of This Species

2015 ◽  
Vol 60 (1) ◽  
pp. 703-708 ◽  
Author(s):  
Philippe Bidet ◽  
Romain Basmaci ◽  
Julien Guglielmini ◽  
Catherine Doit ◽  
Christelle Jost ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Gram Negative Bacteria ◽  
Kingella Kingae ◽  
Gram Negative ◽  
Content Type ◽  
Lactamase Gene ◽  
First Time ◽  
Integrative And Conjugative Element

ABSTRACTWe describe the genome of a penicillinase-producingKingella kingaestrain (KWG1), the first to be isolated in continental Europe, whoseblaTEM-1gene was, for the first time in this species, found to be chromosomally inserted. TheblaTEMgene is located in an integrative and conjugative element (ICE) inserted in Met-tRNA and comprising genes that encode resistance to sulfonamides, streptomycin, and tetracycline. This ICE is homologous to resistance-conferring plasmids ofK. kingaeand other Gram-negative bacteria.

scholarly journals Modulation of Kingella kingae Adherence to Human Epithelial Cells by Type IV Pili, Capsule, and a Novel Trimeric Autotransporter

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Eric A. Porsch ◽  
Thomas E. Kehl-Fie ◽  
Joseph W. St. Geme
Keyword(s):  
Epithelial Cells ◽  
Young Children ◽  
Type Iv Pili ◽  
Upper Respiratory Tract ◽  
Respiratory Epithelial Cells ◽  
Kingella Kingae ◽  
Content Type ◽  
Type Iv ◽  
Human Epithelial Cells ◽  
Respiratory Epithelial

ABSTRACTKingella kingaeis an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. Colonization of the posterior pharynx is a key step in the pathogenesis ofK. kingaedisease. Previous work established that type IV pili are necessary forK. kingaeadherence to the respiratory epithelium. In this study, we set out to identify additional factors that influenceK. kingaeinteractions with human epithelial cells. We found that genetic disruption of the gene encoding a predicted trimeric autotransporter protein called Knh (KingellaNhhAhomolog) resulted in reduced adherence to human epithelial cells. In addition, we established thatK. kingaeelaborates a surface-associated polysaccharide capsule that requires a predicted ABC-type transporter export operon calledctrABCDfor surface presentation. Furthermore, we discovered that the presence of a surface capsule interferes with Knh-mediated adherence to human epithelial cells by nonpiliated organisms and that maximal adherence in the presence of a capsule requires the predicted type IV pilus retraction machinery, PilT/PilU. On the basis of the data presented here, we propose a novel adherence mechanism that allowsK. kingaeto adhere efficiently to human epithelial cells while remaining encapsulated and more resistant to immune clearance.IMPORTANCEKingella kingaeis a Gram-negative bacterium that is being recognized increasingly as a cause of joint and bone infections in young children. The pathogenesis of disease due toK. kingaebegins with bacterial colonization of the upper respiratory tract, and previous work established that surface hair-like fibers called type IV pili are necessary forK. kingaeadherence to respiratory epithelial cells. In this study, we set out to identify additional factors that influenceK. kingaeinteractions with respiratory epithelial cells. We discovered a novel surface protein called Knh that mediatesK. kingaeadherence and found that a surface-associated carbohydrate capsule interferes with the Knh-mediated adherence of organisms lacking pili. Further analysis revealed that pilus retraction is necessary for maximal Knh-mediated adherence in the presence of the capsule. Our results may lead to new strategies to prevent disease due toK. kingaeand potentially other pathogenic bacteria.

scholarly journals Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Marjan M. Hashemi ◽  
John Rovig ◽  
Scott Weber ◽  
Brian Hilton ◽  
Mehdi M. Forouzan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Peptides ◽  
Lipid A ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACT The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and antimicrobial peptides (AMPs) suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs and that lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. These results suggest that there are differences in the resistance mechanisms to colistin and ceragenins/AMPs.

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