scholarly journals Broad-Spectrum Inhibitor of Bacterial Polyphosphate Homeostasis Attenuates Virulence Factors and Helps Reveal Novel Physiology of Klebsiella pneumoniae and Acinetobacter baumannii

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathan Roberge ◽  
Nolan Neville ◽  
Katya Douchant ◽  
Curtis Noordhof ◽  
Nadejda Boev ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Broad Spectrum ◽  
Attractive Alternative ◽  
Microbial Biodiversity ◽  
Human Gut ◽  
Antibiotic Resistant ◽  
Dual Specificity ◽  
Promising Avenue

Acinetobacter baumannii and Klebsiella pneumoniae currently rank amongst the most antibiotic-resistant pathogens, responsible for millions of infections each year. In the wake of this crisis, anti-virulence therapeutics targeting bacterial polyphosphate (polyP) homeostasis have been lauded as an attractive alternative to traditional antibiotics. In this work, we show that the small molecule gallein, a known G-protein βγ subunit modulator, also recently proven to have dual-specificity polyphosphate kinase (PPK) inhibition in Pseudomonas aeruginosa, in turn exhibits broad-spectrum PPK inhibition in other priority pathogens. Gallein treatment successfully attenuated virulence factors of K. pneumoniae and A. baumannii including biofilm formation, surface associated motility, and offered protection against A. baumannii challenge in a Caenorhabditis elegans model of infection. This was highlighted most importantly in the critically understudied A. baumannii, where gallein treatment phenocopied a ppk1 knockout strain of a previously uncharacterized PPK1. Subsequent analysis revealed a unique instance of two functionally and phenotypically distinct PPK1 isoforms encoded by a single bacterium. Finally, gallein was administered to a defined microbial community comprising over 30 commensal species of the human gut microbiome, demonstrating the non-disruptive properties characteristic of anti-virulence treatments as microbial biodiversity was not adversely influenced. Together, these results emphasize that gallein is a promising avenue for the development of broad-spectrum anti-virulence therapeutics.

Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination

2019 ◽  
Vol 69 (11) ◽  
pp. 2015-2018 ◽  
Author(s):  
Ran Nir-Paz ◽  
Daniel Gelman ◽  
Ayman Khouri ◽  
Brittany M Sisson ◽  
Joseph Fackler ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Successful Treatment ◽  
Positive Culture ◽  
Multidrug Resistant ◽  
Bone Infection ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Extensively Drug Resistant ◽  
Tissue Healing

Abstract A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient’s leg did not have to be amputated and he is undergoing rehabilitation.

scholarly journals Broad-Spectrum Cephalosporin-Resistant and/or Fluoroquinolone-Resistant Enterobacterales Associated with Canine and Feline Urogenital Infections

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 387 ◽  
Author(s):  
Igor Loncaric ◽  
Dusan Misic ◽  
Michael P. Szostak ◽  
Frank Künzel ◽  
Sabine Schäfer-Somi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Virulence Factors ◽  
Broad Spectrum ◽  
Virulence Genes ◽  
Enterobacter Cloacae ◽  
Phylogenetic Group ◽  
E Coli ◽  
Urogenital Infections ◽  
Carbapenem Resistant

The aim of the present study was to characterize Enterobacterales resistant to 3rd and 4th generation cephalosporins, carbapenems and/or fluoroquinolones, isolated from dogs and cats with urogenital infections. In total, 36 strains (Escherichia coli (n = 28), Klebsiella pneumoniae (n = 3), Serratia marcescens, Raoultella ornithinolytica, Proteus mirabilis, Citrobacter portucalensis and Enterobacter cloacae (each n = 1)) were included in the present study, 28 from Austria and 8 from Serbia. Isolates were characterized by a polyphasic approach including susceptibility pheno- and genotyping and microarray-based assays. Escherichia (E.) coli isolates were additionally characterized by two-locus (fumC and fimH) sequence phylotyping and multi-locus sequence typing (MLST) of selected isolates. MLST of carbapenem-resistant Enterobacter cloacae isolates was also performed. Among E. coli, the most dominant phylogenetic group was B1 (27.8%), followed by C, (16.6%), A and Clade II (5.5% each), B2 and F (2.77% each). The most predominant β-lactam resistance genes were blaTEM (70%) and blaCTX-M (38.8%), blaCMY (25%). blaNDM was detected in one carbapenem-resistant Enterobacter cloacae ST114. The most common ST among selected E. coli was 744 (10.7% isolates). The pandemic clones ST131 and ST648 carrying CTX-M-15 were also detected. Remaining STs belonged to 469, 1287, 1463 and 1642. E. coli clonotyping revealed 20 CH types. Based on the presence of certain virulence genes, three isolates were categorized as ExPEC/UPEC. The most prevalent virulence factors were fimH detected in 61%, iucD and iss both in 55%, iroN in 27.8%, papC in 13.8% and sat in 8.3% isolates.

Análise da eficácia da higiene oral de pacientes internados em unidade de terapia intensiva em um hospital de alta complexidade do sul do Brasil

2019 ◽  
Vol 31 (2) ◽  
pp. 134
Author(s):  
Karoline Cândido Francisco Teixeira ◽  
Luana Moretti dos Santos ◽  
Fabiano Goulart Azambuja
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Terapia Intensiva

Introdução: As infecções orais, na Unidade de Terapia Intensiva (UTI), deveriam ser preocupações constantes dos profissionais da área da Saúde ali inseridos, devido às consequências que podem causar na saúde geral dos pacientes debilitados sistemicamente. A criação de um protocolo padrão de higiene oral é de suma importância para impedir ou tratar tais infecções, o que possibilita ao paciente conforto e qualidade de vida, devendo ser realizada por profissionais qualificados. Métodos: Foi realizado um estudo transversal e descritivo, cuja análise foi descritiva e se desenvolveu na Unidade de Terapia Intensiva de um hospital de alta complexidade no Sul do Brasil, no período de fevereiro de 2016 a fevereiro de 2017. A amostra total foi composta por 35 pacientes, com idade mínima de 18 anos, que estavam internados na UTI do referido hospital, portadores de prontuários e Termo de Consentimento Livre e Esclarecido. Resultados: Dentre os microrganismos achados nos exames laboratoriais dos pacientes, apresentaram-se em maior quantidade Klebsiella pneumoniae, Staphylococcus coagulase negativo e Escherichia coli. Apenas dois pacientes adquiriram o Acinetobacter baumannii. A maioria dos pacientes obtiveram bactérias gram-negativas presentes em sua microbiota oral. Conclusões: As bactérias patogênicas presentes no meio oral devem ser tratadas e erradicadas. Isso pode ser alcançado por meio de um protocolo padrão de higiene oral. A participação da Odontologia na equipe multidisciplinar no ambiente hospitalar é de fundamental importância para a indicação da terapêutica adequada.

scholarly journals Prevalence and Characterization of Extended-Spectrum β-Lactamase-Producing Antibiotic-Resistant Escherichia coli and Klebsiella pneumoniae in Ready-to-Eat Street Foods

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 850
Author(s):  
Shobha Giri ◽  
Vaishnavi Kudva ◽  
Kalidas Shetty ◽  
Veena Shetty
Keyword(s):  
Escherichia Coli ◽  
Food Safety ◽  
Klebsiella Pneumoniae ◽  
Rural Areas ◽  
Significant Risk ◽  
Microbiological Quality ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Extended Spectrum

As the global urban populations increase with rapid migration from rural areas, ready-to-eat (RTE) street foods are posing food safety challenges where street foods are prepared with less structured food safety guidelines in small and roadside outlets. The increased presence of extended-spectrum-β-lactamase (ESBL) producing bacteria in street foods is a significant risk for human health because of its epidemiological significance. Escherichia coli and Klebsiella pneumoniae have become important and dangerous foodborne pathogens globally for their relevance to antibiotic resistance. The present study was undertaken to evaluate the potential burden of antibiotic-resistant E. coli and K. pneumoniae contaminating RTE street foods and to assess the microbiological quality of foods in a typical emerging and growing urban suburb of India where RTE street foods are rapidly establishing with public health implications. A total of 100 RTE food samples were collected of which, 22.88% were E. coli and 27.12% K. pneumoniae. The prevalence of ESBL-producing E. coli and K. pneumoniae was 25.42%, isolated mostly from chutneys, salads, paani puri, and chicken. Antimicrobial resistance was observed towards cefepime (72.9%), imipenem (55.9%), cefotaxime (52.5%), and meropenem (16.9%) with 86.44% of the isolates with MAR index above 0.22. Among β-lactamase encoding genes, blaTEM (40.68%) was the most prevalent followed by blaCTX (32.20%) and blaSHV (10.17%). blaNDM gene was detected in 20.34% of the isolates. This study indicated that contaminated RTE street foods present health risks to consumers and there is a high potential of transferring multi-drug-resistant bacteria from foods to humans and from person to person as pathogens or as commensal residents of the human gut leading to challenges for subsequent therapeutic treatments.

High frequency of blaPER-1 gene in clinical strains of Acinetobacter baumannii and its association with quorum sensing and virulence factors

Gene Reports ◽  
2021 ◽  
Vol 24 ◽  
pp. 101232
Author(s):  
Fariba Naeimi Mazraeh ◽  
Alka Hasani ◽  
Javid Sadeghi ◽  
Hossein Samadi Kafil ◽  
Mohammad Hossein Soroush Barhaghi ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
High Frequency ◽  
Clinical Strains

scholarly journals Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Atp Synthesis ◽  
Bloodstream Infections ◽  
Model Systems ◽  
Phenotypic Traits ◽  
Virulence Determinants ◽  
Expression Of Genes

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

scholarly journals 1564. Activity of bacteriophage against multidrug resistant Klebsiella pneumoniae

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Sailaja Puttagunta ◽  
Maya Kahan-Haanum ◽  
Sharon Kredo-Russo ◽  
Eyal Weinstock ◽  
Efrat Khabra ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Unmet Need ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Extended Spectrum Beta Lactamase ◽  
Novel Approach ◽  
Infection Types

Abstract Background The prevalence of extended-spectrum beta-lactamase (ESBL) producing and carbapenem resistant (CR) Klebsiella pneumoniae (KP) has significantly risen in all geographic regions. Infections due to these bacteria are associated with high mortality across different infection types. Even with newer options, there remains an unmet need for safe and effective therapeutic options to treat infections caused by ESBL and CR KP. Phage therapy offers a novel approach with an unprecedented and orthogonal mechanism of action for treatment of diseases caused by pathogenic bacterial strains that are insufficiently addressed by available antibiotics. Phage-based therapies confer a high strain-level specificity and have a strong intrinsic safety profile. Here we describe the identification of novel phages that can effectively target antibiotic resistant KP strains. Host range of the 21 phages on 33 strain KP panel via solid culture infectivity assays. Red marks resistance to infection while sensitivity to phage is marked in green Methods KP clinical strains were isolated from human stool specimens preserved in glycerol. Selective culturing was carried, followed by testing of individual colonies for motility, indole and urease production, sequenced and analyzed by Kleborate tool to determine antibiotic resistant genes. Natural phages were isolated from plaques that developed on susceptible bacterial targets, sequenced and characterized. Results Antibiotic-resistant KP strains encoding beta lactamase genes or a carbapenemase (n=33) were isolated from healthy individuals (n=3), and patients with inflammatory bowel disease (n=26) or primary sclerosing cholangitis (n=3). Isolates sequencing revealed bla CTX-M15 and/or bla SHV encoding strains and carbapenamase KPC-2. A panel of 21 phages targeting the beta-lactamase- and carbapenemase-producing KP strains were identified. Phage sequencing revealed that all phages belong to the Caudovirales order and include 6 Siphoviridae, 14 Myoviridae, and 1 Podoviridae. In vitro lytic activity of the phages was tested on the isolated bacteria and revealed a coverage of 70% of the 33 isolated antibiotic resistant strains, >50% of which were targeted by multiple phages. Conclusion Collectively, these results demonstrate the feasibility of identifying phage with potent activity against antibiotic resistant KP strains, and may provide a novel therapeutic approach for treatment of ESBL and CR KP infections. Disclosures All Authors: No reported disclosures

scholarly journals Broad Spectrum Antibiotic Xanthocillin X Effectively Kills Acinetobacter baumannii via Dysregulation of Heme Biosynthesis

2021 ◽  
Author(s):  
Ines Hübner ◽  
Justin A. Shapiro ◽  
Jörn Hoßmann ◽  
Jonas Drechsel ◽  
Stephan M. Hacker ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Broad Spectrum ◽  
Heme Biosynthesis ◽  
Broad Spectrum Antibiotic

scholarly journals Time-Resolved Transcriptional Profiling of Epithelial Cells Infected by Intracellular Acinetobacter baumannii

2021 ◽  
Vol 9 (2) ◽  
pp. 354
Author(s):  
Nuria Crua Asensio ◽  
Javier Macho Rendón ◽  
Marc Torrent Burgas
Keyword(s):  
Acinetobacter Baumannii ◽  
Transcriptional Profiling ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Time Resolved ◽  
Antibiotic Resistant ◽  
Common Features ◽  
Profile Changes

The rise in the number of antibiotic-resistant bacteria has become a serious threat to health, making it important to identify, characterize and optimize new molecules to help us to overcome the infections they cause. It is well known that Acinetobacter baumannii has a significant capacity to evade the actions of antibacterial drugs, leading to its emergence as one of the bacteria responsible for hospital and community-acquired infections. Nonetheless, how this pathogen infects and survives inside the host cell is unclear. In this study, we analyze the time-resolved transcriptional profile changes observed in human epithelial HeLa cells after infection by A. baumannii, demonstrating how it survives in host cells and starts to replicate 4 h post infection. These findings were achieved by sequencing RNA to obtain a set of Differentially Expressed Genes (DEGs) to understand how bacteria alter the host cells’ environment for their own benefit. We also determine common features observed in this set of genes and identify the protein–protein networks that reveal highly-interacted proteins. The combination of these findings paves the way for the discovery of new antimicrobial candidates for the treatment of multidrug-resistant bacteria.

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