Anatomy of an extensively drug-resistant outbreak in Tuscany, Italy.

A protracted outbreak of New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics.

An Assessment of Siderophore Production, Mucoviscosity, and Mouse Infection Models for Defining the Virulence Spectrum of Hypervirulent Klebsiella pneumoniae.

Hypervirulent (hvKp) bacteria are more virulent than classical (cKp) with resultant differences in clinical manifestations and management. It is unclear whether all hvKp isolates share a similar pathogenic potential. This report assessed the utility of siderophore production, mucoviscosity, and murine infection for defining the virulence spectrum of hvKp.

An Evaluation of BfmR-Regulated Antimicrobial Resistance in the Extensively Drug Resistant (XDR) Strain HUMC1.

is a problematic pathogen due to its common expression of extensive drug resistance (XDR) and ability to survive in the healthcare environment. These characteristics are mediated, in part, by the signal transduction system BfmR/BfmS. We previously demonstrated, in antimicrobial sensitive clinical isolates, that BfmR conferred increased resistance to meropenem and polymyxin E.

The Galleria mellonella Infection Model Does Not Accurately Differentiate between Hypervirulent and Classical Klebsiella pneumoniae.

Hypervirulent (hvKp) is an emerging pathogen of increasing concern due to its ability to cause serious organ and life-threatening infections in healthy individuals and its increasing acquisition of antimicrobial resistance determinants. Identification of hvKp is critical for patient care and epidemiologic and research studies. Five genotypic markers on the hvKp-specific virulence plasmid can accurately differentiate hvKp from the less virulent classical (cKp) strain, but it is unclear whether the possession of fewer markers accurately predicts the hvKp pathotype.

Antibody Dependent Enhancement of Infection in a Mouse Pneumonia Model.

has become a pathogen of increasing medical importance because of the emergence of multidrug-resistant strains and the high rate of mortality of infected patients. Promising animal study results have been reported recently with active and passive immunization against virulence factors. In the present study, a monoclonal IgG3 antibody, 8E3, was developed with specificity for the K2 capsular polysaccharide of , and its therapeutic potential was assessed.

Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae.

A hypervirulent (hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical (cKp) infections, hvKp causes tissue-invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies.

The Capsular Polysaccharide of Acinetobacter baumannii Is an Obstacle for Therapeutic Passive Immunization Strategies.

has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606.

Metabolite Transporter PEG344 Is Required for Full Virulence of Hypervirulent Klebsiella pneumoniae Strain hvKP1 after Pulmonary but Not Subcutaneous Challenge.

Hypervirulent (hvKP) is an emerging pathotype that is capable of causing tissue-invasive and organ- and life-threatening infections in healthy individuals from the community. Knowledge on the virulence factors specific to hvKP is limited. In this report, we describe a new factor (PEG344) that increases the virulence of hvKP strain hvKP1.

The Response Regulator BfmR Is a Potential Drug Target for Acinetobacter baumannii.

Identification and validation is the first phase of target-based antimicrobial development. BfmR (RstA), a response regulator in a two-component signal transduction system (TCS) in Acinetobacter baumannii, is an intriguing potential antimicrobial target. A unique characteristic of BfmR is that its inhibition would have the dual benefit of significantly decreasing in vivo survival and increasing sensitivity to selected antimicrobials.

Structure of shikimate kinase, an in vivo essential metabolic enzyme in the nosocomial pathogen Acinetobacter baumannii, in complex with shikimate.

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that is an important cause of healthcare-associated infections exhibiting high mortality rates. Clinical isolates of multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii strains are increasingly being observed.

Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo.

The siderophore aerobactin is the dominant siderophore produced by hypervirulent Klebsiella pneumoniae (hvKP) and was previously shown to be a major virulence factor in systemic infection. However, strains of hvKP commonly produce the additional siderophores yersiniabactin, salmochelin, and enterobactin. The roles of these siderophores in hvKP infection have not been optimally defined.

Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae.

Hypervirulent (hypermucoviscous) Klebsiella pneumoniae (hvKP) strains are an emerging variant of "classical" K. pneumoniae (cKP) that cause organ and life-threatening infection in healthy individuals. An understanding of hvKP-specific virulence mechanisms that enabled evolution from cKP is limited.

The K1 capsular polysaccharide from Acinetobacter baumannii is a potential therapeutic target via passive immunization.

The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target.

In vivo-validated essential genes identified in Acinetobacter baumannii by using human ascites overlap poorly with essential genes detected on laboratory media.

Unlabelled: A critical feature of a potential antimicrobial target is the characteristic of being essential for growth and survival during host infection. For bacteria, genome-wide essentiality screens are usually performed on rich laboratory media. This study addressed whether genes detected in that manner were optimal for the identification of antimicrobial targets since the in vivo milieu is fundamentally different.

Biofilm formed by a hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae does not enhance serum resistance or survival in an in vivo abscess model.

A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP. It has been shown that hvKP strains produce more biofilm than "classical" stains of K.

Hypervirulent K. pneumoniae secretes more and more active iron-acquisition molecules than "classical" K. pneumoniae thereby enhancing its virulence.

Background: A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP compared to "classic" K. pneumoniae (cKP).

The K1 capsular polysaccharide of Acinetobacter baumannii strain 307-0294 is a major virulence factor.

Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii.

Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumannii in vitro and in vivo.

Background: Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about genes important for its survival in vivo.

Methods And Results: Screening of random transposon mutants of the model pathogen AB307-0294 identified the mutant AB307.

Capsular polysaccharide and the O-specific antigen impede antibody binding: a potential obstacle for the successful development of an extraintestinal pathogenic Escherichia coli vaccine.

Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide variety of infections that are responsible for significant morbidity, mortality and costs to our healthcare system. An efficacious vaccine against ExPEC would be desirable. Previously, we demonstrated that nasal immunization with a genetically engineered strain in which capsule and O-antigen are no longer expressed (CP923) was immunogenic, generated antibodies that bound a subset of heterologous ExPEC strains, and enhanced neutrophil-mediated bactericidal activity against the homologous and a heterologous strain in vitro.

Rat pneumonia and soft-tissue infection models for the study of Acinetobacter baumannii biology.

Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about its mechanisms of pathogenesis, and safe reliable agents with predictable activity against A. baumannii are presently nonexistent.

A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate.

Infections due to extraintestinal pathogenic E. coli (ExPEC) result in significant morbidity, mortality and increased healthcare costs. An efficacious vaccine against ExPEC would be desirable.

E. coli virulence factor hemolysin induces neutrophil apoptosis and necrosis/lysis in vitro and necrosis/lysis and lung injury in a rat pneumonia model.

Enteric gram-negative bacilli, such as Escherichia coli are the most common cause of nosocomial pneumonia. In this study a wild-type extraintestinal pathogenic strain of E. coli (ExPEC)(CP9) and isogenic derivatives deficient in hemolysin (Hly) and cytotoxic necrotizing factor (CNF) were assessed in vitro and in a rat model of gram-negative pneumonia to test the hypothesis that these virulence factors induce neutrophil apoptosis and/or necrosis/lysis.