scholarly journals Regulation of Pulmonary Bacterial Immunity by Follistatin-Like Protein 1

2020 ◽  
Vol 89 (1) ◽  
pp. e00298-20
Author(s):  
Matthew Henkel ◽  
Justin A. Dutta ◽  
Jessica Partyka ◽  
Taylor Eddens ◽  
Raphael Hirsch ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Immune Cell ◽  
Lung Burden ◽  
Antibiotic Resistant ◽  
Γδt Cells ◽  
Content Type ◽  
Interleukin 17A ◽  
Infectious Burden ◽  
Lung Immunity

ABSTRACTKlebsiella pneumoniae is a common cause of antibiotic-resistant pneumonia. Follistatin-like protein 1 (FSTL-1) is highly expressed in the lung and is critical for lung homeostasis. The role of FSTL-1 in immunity to bacterial pneumonia is unknown. Wild-type (WT) and FSTL-1 hypomorphic (Hypo) mice were infected with Klebsiella pneumoniae to determine infectious burden, immune cell abundance, and cytokine production. FSTL-1 Hypo/TCRδ−/− and FSTL-1 Hypo/IL17ra−/− were also generated to assess the role of γδT17 cells in this model. FSTL-1 Hypo mice had reduced K. pneumoniae lung burden compared with that of WT controls. FSTL-1 Hypo mice had increased Il17a/interleukin-17A (IL-17A) and IL-17-dependent cytokine expression. FSTL-1 Hypo lungs also had increased IL-17A+ and TCRγδ+ cells. FSTL-1 Hypo/TCRδ−/− displayed a lung burden similar to that of FSTL-1 Hypo and reduced lung burden compared with the TCRδ−/− controls. However, FSTL-1 Hypo/TCRδ−/− mice had greater bacterial dissemination than FSTL-1 Hypo mice, suggesting that gamma delta T (γδT) cells are dispensable for FSTL-1 Hypo control of pulmonary infection but are required for dissemination control. Confusing these observations, FSTL-1 Hypo/TCRδ−/− lungs had an increased percentage of IL-17A-producing cells compared with that of TCRδ−/− mice. Removal of IL-17A signaling in the FSTL-1 Hypo mouse resulted in an increased lung burden. These findings identify a novel role for FSTL-1 in innate lung immunity to bacterial infection, suggesting that FSTL-1 influences type-17 pulmonary bacterial immunity.

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 Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice

2011 ◽  
Vol 79 (11) ◽  
pp. 4503-4510 ◽  
Author(s):  
Takashi Dejima ◽  
Kensuke Shibata ◽  
Hisakata Yamada ◽  
Hiromitsu Hara ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Γδ T Cells ◽  
Protective Role ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Content Type ◽  
Naturally Occurring ◽  
Interleukin 17A

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

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 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.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Myophage Muenster

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Cody Martin ◽  
Lauren Lessor ◽  
James Clark ◽  
Tram Le ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Nosocomial Infections ◽  
Complete Genome Sequence ◽  
Protein Coding ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Putative Protein ◽  
Protein Coding Genes ◽  
Tail Fibers

ABSTRACT Klebsiella pneumoniae is associated with antibiotic-resistant nosocomial infections. Here, we present the annotated genome sequence of the Klebsiella jumbo phage Muenster. The Muenster genome sequence (346,937 bp) encodes 6 tRNAs and 561 putative protein-coding genes, including 9 tail fibers, suggesting a genetic mechanism to broaden the host range.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Siphophage Skenny

2019 ◽  
Vol 8 (39) ◽  
Author(s):  
Jacob Gramer ◽  
Sarah Kenny ◽  
Heather Newkirk ◽  
Mei Liu ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Nosocomial Infections ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Opportunistic Pathogen ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Content Type

Klebsiella pneumoniae is a Gram-negative opportunistic pathogen and a leading cause of antibiotic-resistant nosocomial infections. The genome sequence of siphophage Skenny, which infects K. pneumoniae, is described here. Skenny encodes 78 genes and is closely related to Klebsiella phages KPN N141 and MezzoGao, which are T1-like phages.

scholarly journals Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Hea-Jin Jung ◽  
Eric R. Littmann ◽  
Ruth Seok ◽  
Ingrid M. Leiner ◽  
Ying Taur ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genetic Factors ◽  
Intestinal Lumen ◽  
Intestinal Colonization ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Gut Colonization ◽  
Colonization Factors

ABSTRACT A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp. Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-Kp. IMPORTANCE Klebsiella pneumoniae is a common cause of bloodstream infections in immunocompromised and hospitalized patients, and over the last 2 decades, some strains have acquired resistance to nearly all available antibiotics, including broad-spectrum carbapenems. The U.S. Centers for Disease Control and Prevention has listed carbapenem-resistant K. pneumoniae (CR-Kp) as an urgent public health threat. Dense colonization of the intestine by CR-Kp and other antibiotic-resistant bacteria is associated with an increased risk of bacteremia. Reducing the density of gut colonization by CR-Kp is likely to reduce their transmission from patient to patient in health care facilities as well as systemic infections. How CR-Kp expands and persists in the gut lumen, however, is poorly understood. Herein, we generated a highly saturated mutant library in a multidrug-resistant K. pneumoniae strain and identified genetic factors that are associated with dense gut colonization by K. pneumoniae. This study sheds light on host colonization by K. pneumoniae and identifies potential colonization factors that contribute to high-density persistence of K. pneumoniae in the intestine.

scholarly journals An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Possesses Five Tandem Repeats of the blaKPC-2::NTEKPC-Id Fragment

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Ning Dong ◽  
Lizhang Liu ◽  
Rong Zhang ◽  
Kaichao Chen ◽  
Miaomiao Xie ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Klebsiella Pneumoniae ◽  
Tandem Repeats ◽  
Dna Recombination ◽  
Multidrug Resistant ◽  
Plasmid Evolution ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT Completed sequences of three plasmids from a carbapenem-resistant hypervirulent Klebsiella pneumoniae isolate, SH9, were obtained. In addition to the pLVPK-like virulence-conferring plasmid (pVir-CR-HvKP_SH9), the two multidrug-resistant plasmids (pKPC-CR-HvKP4_SH9 and pCTX-M-CR-HvKP4_SH9) were predicted to originate from a single pKPC-CR-HvKP4-like multireplicon plasmid through homologous recombination. Interestingly, the blaKPC-2 gene was detectable in five tandem repeats exhibiting the format of an NTEKPC-Id-like transposon (IS26-ΔTn3-ISKpn8-blaKPC-2-ΔISKpn6-korC-orf-IS26). The data suggest an important role of DNA recombination in mediating active plasmid evolution.

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