Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort.

Background: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp.

Semisynthetic Glycoconjugate Vaccine Lead against Serotype O2afg Induces Functional Antibodies and Reduces the Burden of Acute Pneumonia.

Carbapenem-resistant (CR-) bacteria are a serious global health concern due to their drug-resistance to nearly all available antibiotics, fast spread, and high mortality rate. O2afg is a major CR- serotype in the sequence type 258 group (KPST258) that is weakly immunogenic in humans. Here, we describe the creation and evaluation of semisynthetic O2afg glycoconjugate vaccine leads containing one and two repeating units of the polysaccharide epitope that covers the surface of the bacteria conjugated to the carrier protein CRM.

Carbapenem-resistant Enterobacterales in solid organ transplant recipients.

Carbapenem-resistant Enterobacterales (CRE) are an important threat to the health of solid organ transplant recipients (SOTr); data comparing outcomes of SOTr with CRE to non-SOTr with CRE are lacking. A matched cohort study was performed within 2 prospective, multicenter, cohort studies (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales and Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales 2). The epidemiology, desirability of outcome rankings outcomes, and mortality of SOTr and non-SOTr hospitalized in the United States (December 2011-August 2017) with clinical isolates with Centers for Disease Control and Prevention-defined CRE were compared.

Direct Mapping of Polyclonal Epitopes in Serum by HDX-MS.

Elucidating the interactions that drive antigen recognition is central to understanding antibody-mediated protection and is vital for the rational design of immunogens. Often, structural knowledge of epitopes targeted by antibodies is derived from isolated studies of monoclonal antibodies, for which numerous structural techniques exist. In contrast, there are very few approaches capable of mapping the full scope of antigen surfaces targeted by polyclonal sera through the course of a natural antibody response.

With age comes resilience: how mitochondrial modulation drives age-associated fluconazole tolerance in .

Unlabelled: () is an opportunistic fungal microorganism that causes life-threatening meningoencephalitis. During the infection, the microbial population is heterogeneously composed of cells with varying generational ages, with older cells accumulating during chronic infections. This is attributed to their enhanced resistance to phagocytic killing and tolerance of antifungals like fluconazole (FLC).

Distinct effect of calorie restriction between congenic mating types of Cryptococcus neoformans.

Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells.

Measuring Replicative Lifespan in Cryptococcus neoformans.

Advances in understanding cellular aging research have been possible due to the analysis of the replicative lifespan of yeast cells. Studying longevity in the pathogenic yeast Cryptococcus neoformans is essential because old yeast cells with age-related phenotypes accumulate during infection and are associated with increased virulence and antifungal tolerance. Microdissection and microfluidic devices are valuable tools for continuously tracking cells at the single-cell level.

Host-Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged .

is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood.

Achieving Resilience in Aging: How Mitochondrial Modulation Drives Age-associated Fluconazole Tolerance in .

Unlabelled: ( ) is an opportunistic fungal microorganism that causes life-threatening meningoencephalitis. During the infection, the microbial population is heterogeneously composed of cells with varying generational ages, with older cells accumulating during chronic infections. This is attributed to their enhanced resistance to phagocytic killing and tolerance of antifungals like fluconazole (FLC).

Carbapenem-resistant in Children at 18 US Health Care System Study Sites: Clinical and Molecular Epidemiology From a Prospective Multicenter Cohort Study.

Background: Carbapenem-resistant (CRE) are an urgent public health threat in the United States.

Objective: Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort.

Methods: CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017.

Inactivation of the Sts enzymes promotes resistance to lethal infection.

is a highly infective Gram-positive bacterial pathogen that causes a wide range of diseases in both healthy and immunocompromised individuals. It can evade host immune defenses by expressing numerous virulence factors and toxins. Coupled with the inability of the human host to develop protective immunity against , the emergence of antibiotic-resistant strains complicates treatment options.

Cryptogenic Liver Abscess Caused by a K1 Serotype Isolate.

Hypervirulent (hv) is a common cause of pyogenic liver abscesses in Asia but is quite uncommon in North America. Among the cases described in North America, only occasional reports have described molecular strain typing to confirm the K1 strain as the causative agent. We report a 56-year-old Hispanic female with no previous intra-abdominal pathology and no recent travel, who presented with subacute abdominal pain and developed bacteremia and monomicrobial pyogenic liver abscess due to a community-acquired K1 serotype isolate.

Novel ABC Transporter Associated with Fluconazole Resistance in Aging of .

causes meningoencephalitis in immunocompromised individuals, which is treated with fluconazole (FLC) monotherapy when resources are limited. This can lead to azole resistance, which can be mediated by overexpression of ABC transporters, a class of efflux pumps. ABC pump-mediated efflux of FLC is also augmented in 10-generation old cells.

Patient-Derived Antibody Data Yields Development of Broadly Cross-Protective Monoclonal Antibody against ST258 Carbapenem-Resistant .

The most pressing challenge for the development of anti-capsular antibodies is maximizing coverage against the heterogenous capsular polysaccharide (CPS) of carbapenem-resistant Klebsiella pneumoniae (CR-). So far, only CR- with CPS has been successfully targeted by antibodies. Here, we present murine antibody 24D11, which was developed by vaccinating mice with purified -type CPS.

Accessory Genomes Drive Independent Spread of Carbapenem-Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX.

Carbapenem-resistant Klebsiella pneumoniae (CR) is an urgent public health threat. Worldwide dissemination of CR has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CR CG307 lineage.

Replicative Aging Remodels the Cell Wall and Is Associated with Increased Intracellular Trafficking in Human Pathogenic Yeasts.

Replicative aging is an underexplored field of research in medical mycology. Cryptococcus neoformans () and Candida glabrata () are dreaded fungal pathogens that cause fatal invasive infections. The fungal cell wall is essential for yeast viability and pathogenesis.

Bacterial infections and death among patients with Covid-19 versus non Covid-19 patients with pneumonia.

Background: Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with 'pneumonia' the year previously.

Low Glucose Mediated Fluconazole Tolerance in .

Chronic meningoencephalitis is caused by and is treated in many parts of the world with fluconazole (FLC) monotherapy, which is associated with treatment failure and poor outcome. In the host, propagates predominantly under low glucose growth conditions. We investigated whether low glucose, mimicked by growing in synthetic media (SM) with 0.

A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro.

We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif at its polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superantigenic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by interfering with the proteolytic activity of cell proteases (furin and TMPRSS2).

Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients.

Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant (CR-) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR--infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR- cultures.

Prevalence of IgM and IgG antibodies to SARS-CoV-2 in health care workers at a tertiary care New York hospital during the Spring COVID-19 surge.

Background: Health care workers (HCW) such as anesthesiologists, surgeons, and intensivists face high rates of exposure to SARS-CoV-2 through direct contact with COVID-19 patients. While there are initial reports of the prevalence of COVID-19 antibodies among the general population, there are few reports comparing the seroprevalence of IgM/IgG COVID-19 antibodies in HCW of different exposure levels as well as different HCW professions.

Methods: A convenience sample of health care workers provided blood for COVID-19 antibody testing and a review of medical history and work exposure for correlative analyses.

Replicative Aging in Pathogenic Fungi.

, , , and are pathogenic yeasts which can cause systemic infections in immune-compromised as well as immune-competent individuals. These yeasts undergo replicative aging analogous to a process first described in the nonpathogenic yeast . The hallmark of replicative aging is the asymmetric cell division of mother yeast cells that leads to the production of a phenotypically distinct daughter cell.

A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry .

We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral motif, and in particular its PRRA insert, to inhibit infection by blocking the access of host cell proteases, TMPRSS2 or furin, to the cleavage site. The high affinity of 6D3 for the furin-cleavage site originates from a poly-acidic segment at its heavy chain CDR2, a feature shared with SARS-CoV-2-neutralizing mAb 4A8.