scholarly journals High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung

2017 ◽  
Vol 86 (2) ◽  
Author(s):  
David A. Rosen ◽  
Joy Twentyman ◽  
David A. Hunstad
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pathogenic Bacteria ◽  
Host Responses ◽  
Potential Therapeutic Target ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Bacterial Physiology ◽  
Type 1 Pili ◽  
Type 3

ABSTRACTThe bacterial second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) has been shown to influence the expression of virulence factors in certain pathogenic bacteria, but little is known about its activity in the increasingly antibiotic-resistant pathogenKlebsiella pneumoniae. Here, the expression inK. pneumoniaeof a heterologous diguanylate cyclase increased the bacterial c-di-GMP concentration and attenuated pathogenesis in murine pneumonia. This attenuation remained evident in mice lacking the c-di-GMP sensor STING, indicating that the high c-di-GMP concentration exerted its influence not on host responses but on bacterial physiology. While serum resistance and capsule expression were unaffected by the increased c-di-GMP concentration, both type 3 and type 1 pili were strongly upregulated. Importantly, attenuation ofK. pneumoniaevirulence by high c-di-GMP levels was abrogated when type 1 pilus expression was silenced. We conclude that increased type 1 piliation may hamperK. pneumoniaevirulence in the respiratory tract and that c-di-GMP signaling represents a potential therapeutic target for antibiotic-resistantK. pneumoniaein this niche.

scholarly journals Role of Klebsiella pneumoniae Type 1 and Type 3 Fimbriae in Colonizing Silicone Tubes Implanted into the Bladders of Mice as a Model of Catheter-Associated Urinary Tract Infections

2013 ◽  
Vol 81 (8) ◽  
pp. 3009-3017 ◽  
Author(s):  
Caitlin N. Murphy ◽  
Martin S. Mortensen ◽  
Karen A. Krogfelt ◽  
Steven Clegg
Keyword(s):  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Wild Type ◽  
Content Type ◽  
Tract Infections ◽  
Type 3

ABSTRACTCatheter-associated urinary tract infections are biofilm-mediated infections that cause a significant economic and health burden in nosocomial environments. Using a newly developed murine model of this type of infection, we investigated the role of fimbriae in implant-associated urinary tract infections by the Gram-negative bacteriumKlebsiella pneumoniae, which is a proficient biofilm former and a commonly isolated nosocomial pathogen. Studies have shown that type 1 and type 3 fimbriae are involved in attachment and biofilm formationin vitro, and these fimbrial types are suspected to be important virulence factors during infection. To test this hypothesis, the virulence of fimbrial mutants was assessed in independent challenges in which mouse bladders were inoculated with the wild type or a fimbrial mutant and in coinfection studies in which the wild type and fimbrial mutants were inoculated together to assess the results of a direct competition in the urinary tract. Using these experiments, we were able to show that both fimbrial types serve to enhance colonization and persistence. Additionally, a double mutant had an additive colonization defect under some conditions, indicating that both fimbrial types have unique roles in the attachment and persistence in the bladder and on the implant itself. All of these mutants were outcompeted by the wild type in coinfection experiments. Using these methods, we are able to show that type 1 and type 3 fimbriae are important colonization factors in the murine urinary tract when an implanted silicone tube is present.

scholarly journals Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Approaches ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surface Polysaccharides ◽  
Resistant Strains ◽  
Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Myophage May

2019 ◽  
Vol 8 (19) ◽  
Author(s):  
Katherine T. Nguyen ◽  
Rachele Bonasera ◽  
Garret Benson ◽  
Adriana C. Hernandez-Morales ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Resistant Strains

May is a newly isolated myophage that infects multidrug-resistant strains of Klebsiella pneumoniae, a pathogen that is associated with antibiotic-resistant infections in humans. The genome of May has been shown to be similar to that of phage Vi01.

scholarly journals Comprehensive Identification of Fim-Mediated Inversions in UropathogenicEscherichia coliwith Structural Variation Detection Using Relative Entropy

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Colin W. Russell ◽  
Rashmi Sukumaran ◽  
Lu Ting Liow ◽  
Balamurugan Periaswamy ◽  
Shazmina Rafee ◽  
...  
Keyword(s):  
Relative Entropy ◽  
Structural Variation ◽  
Infection Type ◽  
Epigenetic Mechanism ◽  
Structural Variations ◽  
Entire Genome ◽  
Content Type ◽  
Type 1 Pili ◽  
Tract Infections

ABSTRACTMost urinary tract infections (UTIs) are caused by uropathogenicEscherichia coli(UPEC), which depends on an extracellular organelle (type 1 pili) for adherence to bladder cells during infection. Type 1 pilus expression is partially regulated by inversion of a piece of DNA referred to asfimS, which contains the promoter for thefimoperon encoding type 1 pili.fimSinversion is regulated by up to five recombinases collectively known as Fim recombinases. These Fim recombinases are currently known to regulate two other switches: theipuSandhyxSswitches. A long-standing question has been whether the Fim recombinases regulate the inversion of other switches, perhaps to coordinate expression for adhesion or virulence. We answered this question using whole-genome sequencing with a newly developed algorithm (structural variation detection using relative entropy [SVRE]) for calling structural variations using paired-end short-read sequencing. SVRE identified all of the previously known switches, refining the specificity of which recombinases act at which switches. Strikingly, we found no new inversions that were mediated by the Fim recombinases. We conclude that the Fim recombinases are each highly specific for a small number of switches. We hypothesize that the unlinked Fim recombinases have been recruited to regulatefimS, andfimSonly, as a secondary locus; this further implies that regulation of type 1 pilus expression (and its role in gastrointestinal and/or genitourinary colonization) is important enough, on its own, to influence the evolution and maintenance of multiple additional genes within the accessory genome ofE. coli.IMPORTANCEUTI is a common ailment that affects more than half of all women during their lifetime. The leading cause of UTIs is UPEC, which relies on type 1 pili to colonize and persist within the bladder during infection. The regulation of type 1 pili is remarkable for an epigenetic mechanism in which a section of DNA containing a promoter is inverted. The inversion mechanism relies on what are thought to be dedicated recombinase genes; however, the full repertoire for these recombinases is not known. We show here that there are no additional targets beyond those already identified for the recombinases in the entire genome of two UPEC strains, arguing that type 1 pilus expression itself is the driving evolutionary force for the presence of these recombinase genes. This further suggests that targeting the type 1 pilus is a rational alternative nonantibiotic strategy for the treatment of UTI.

scholarly journals Molecular Characterization of Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae in the Countries of the Gulf Cooperation Council: Dominance of OXA-48 and NDM Producers

2014 ◽  
Vol 58 (6) ◽  
pp. 3085-3090 ◽  
Author(s):  
Hosam M. Zowawi ◽  
Anna L. Sartor ◽  
Hanan H. Balkhy ◽  
Timothy R. Walsh ◽  
Sameera M. Al Johani ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
United Arab Emirates ◽  
Gulf Cooperation Council ◽  
Mechanisms Of Resistance ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Genes ◽  
Gcc Countries

ABSTRACTThe molecular epidemiology and mechanisms of resistance of carbapenem-resistantEnterobacteriaceae(CRE) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic-resistant genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Sixty-two isolates which screened positive for potential carbapenemase production were assessed, and 45 were found to produce carbapenemase. The most common carbapenemases were of the OXA-48 (35 isolates) and NDM (16 isolates) types; 6 isolates were found to coproduce the OXA-48 and NDM types. No KPC-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with seven clusters of clonally relatedKlebsiella pneumoniae. Awareness of CRE in GCC countries has important implications for controlling the spread of CRE in the Middle East and in hospitals accommodating patients transferred from the region.

scholarly journals The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli

2016 ◽  
Vol 198 (19) ◽  
pp. 2662-2672 ◽  
Author(s):  
Kyle A. Floyd ◽  
Courtney A. Mitchell ◽  
Allison R. Eberly ◽  
Spencer J. Colling ◽  
Ellisa W. Zhang ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Biofilm Formation ◽  
Energy Deficit ◽  
Wild Type ◽  
Content Type ◽  
Anoxic Conditions ◽  
E Coli ◽  
Type 1 Pili ◽  
Tract Infections

ABSTRACTUropathogenicEscherichia coli(UPEC), which causes the majority of urinary tract infections (UTI), uses pilus-mediated adherence to initiate biofilm formation in the urinary tract. Oxygen gradients withinE. colibiofilms regulate expression and localization of adhesive type 1 pili. A transposon mutant screen for strains defective in biofilm formation identified theubiI(formerlyvisC) aerobic ubiquinone synthase gene as critical for UPEC biofilm formation. In this study, we characterized a nonpolarubiIdeletion mutant and compared its behavior to that of wild-type bacteria grown under aerobic and anoxic conditions. Consistent with its function as an aerobic ubiquinone-8 synthase, deletion ofubiIin UPEC resulted in reduced membrane potential, diminished motility, and reduced expression of chaperone-usher pathway pili. Loss of aerobic respiration was previously shown to negatively impact expression of type 1 pili. To determine whether this reduction in type 1 pili was due to an energy deficit, wild-type UPEC and theubiImutant were compared for energy-dependent phenotypes under anoxic conditions, in which quinone synthesis is undertaken by anaerobic quinone synthases. Under anoxic conditions, the two strains exhibited wild-type levels of motility but produced diminished numbers of type 1 pili, suggesting that the reduction of type 1 pilus expression in the absence of oxygen is not due to a cellular energy deficit. Acute- and chronic-infection studies in a mouse model of UTI revealed a significant virulence deficit in theubiImutant, indicating that UPEC encounters enough oxygen in the bladder to induce aerobic ubiquinone synthesis during infection.IMPORTANCEThe majority of urinary tract infections are caused by uropathogenicE. coli, a bacterium that can respire in the presence and absence of oxygen. The bladder environment is hypoxic, with oxygen concentrations ranging from 4% to 7%, compared to 21% atmospheric oxygen. This work provides evidence that aerobic ubiquinone synthesis must be engaged during bladder infection, indicating that UPEC bacteria sense and use oxygen as a terminal electron acceptor in the bladder and that this ability drives infection potential despite the fact that UPEC is a facultative anaerobe.

scholarly journals Role of type 1 and type 3 fimbriae in Klebsiella pneumoniae biofilm formation

2010 ◽  
Vol 10 (1) ◽  
pp. 179 ◽  
Author(s):  
Casper Schroll ◽  
Kim B Barken ◽  
Karen A Krogfelt ◽  
Carsten Struve
Keyword(s):  
Klebsiella Pneumoniae ◽  
Biofilm Formation ◽  
Type 3

scholarly journals Klebsiella pneumoniae: Going on the Offense with a Strong Defense

2016 ◽  
Vol 80 (3) ◽  
pp. 629-661 ◽  
Author(s):  
Michelle K. Paczosa ◽  
Joan Mecsas
Keyword(s):  
Klebsiella Pneumoniae ◽  
Critical Role ◽  
Infection Model ◽  
Interleukin 17 ◽  
Regulation Of Transcription ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Recent Emergence ◽  
Wide Range ◽  
Tract Infections

SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Podophage Pone

2021 ◽  
Vol 10 (21) ◽  
Author(s):  
Johnathan Lo ◽  
Lauren Lessor ◽  
James Clark ◽  
Tram Le ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Phage Therapy ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Content Type

Klebsiella pneumoniae is a Gram-negative pathogen that has become increasingly antibiotic resistant. Phage therapy is potentially a useful approach to control this pathogen. Here, we present the genome sequence of the phiKMV-like K. pneumoniae podophage Pone.

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