Dietary zinc deficiency promotes Acinetobacter baumannii lung infection via IL-13 in mice.

Dietary zinc deficiency is a major risk factor for pneumonia. Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia and a critical public health threat due to increasing rates of multidrug resistance. Patient populations at increased risk for A.

Amino acid competition shapes gut carriage.

Antimicrobial resistance is an urgent threat to human health. Asymptomatic colonization is often critical for persistence of antimicrobial-resistant pathogens. Gut colonization by the antimicrobial-resistant priority pathogen is associated with increased risk of clinical infection.

Genetic synergy between undecaprenyl phosphate biosynthesis and the Mla system impacts cell envelope and antimicrobial resistance.

is a Gram-negative bacterial pathogen that poses a major health concern due to increasing multidrug resistance. The Gram-negative cell envelope is a key barrier to antimicrobial entry and includes an inner and outer membrane. The maintenance of lipid asymmetry (Mla) system is the main homeostatic mechanism by which Gram-negative bacteria maintain outer membrane asymmetry.

Genetic synergy in undecaprenyl biosynthesis and maintenance of lipid asymmetry impacts outer membrane and antimicrobial resistance.

is a Gram-negative healthcare-associated pathogen that poses a major health concern due to increasing multidrug resistance. The Gram-negative cell envelope is a key barrier to antimicrobial entry and includes an inner and outer membrane. The outer membrane has an asymmetric composition that is important for structural integrity and barrier to the environment.

Acinetobacter Metabolism in Infection and Antimicrobial Resistance.

Acinetobacter infections have high rates of mortality due to an increasing incidence of infections by multidrug-resistant (MDR) and extensively-drug-resistant (XDR) strains. Therefore, new therapeutic strategies for the treatment of Acinetobacter infections are urgently needed. Acinetobacter spp.

Mobile genetic elements in Acinetobacter antibiotic-resistance acquisition and dissemination.

Pathogenic Acinetobacter species, most notably Acinetobacter baumannii, are a significant cause of healthcare-associated infections worldwide. Acinetobacter infections are of particular concern to global health due to the high rates of multidrug resistance and extensive drug resistance. Widespread genome sequencing and analysis has determined that bacterial antibiotic resistance is often acquired and disseminated through the movement of mobile genetic elements, including insertion sequences (IS), transposons, integrons, and conjugative plasmids.

Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia.

exposure of multiple Gram-negative bacteria to an aminoglycoside (AG) antibiotic has previously been demonstrated to result in bacterial alterations that interact with host factors to suppress Gram-negative pneumonia. However, the mechanisms resulting in suppression are not known. Here, the hypothesis that Gram-negative bacteria bind and retain AGs, which are introduced into the lung and interact with host defenses to affect bacterial killing, was tested.

Identification of Two Variants of Acinetobacter baumannii Strain ATCC 17978 with Distinct Genotypes and Phenotypes.

Acinetobacter baumannii is a nosocomial pathogen that exhibits substantial genomic plasticity. Here, the identification of two variants of A. baumannii ATCC 17978 that differ based on the presence of a 44-kb accessory locus, named AbaAL44 (A.

Modulating Isoprenoid Biosynthesis Increases Lipooligosaccharides and Restores Acinetobacter baumannii Resistance to Host and Antibiotic Stress.

Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia and a critical threat due to multidrug resistance. The A. baumannii outer membrane is an asymmetric lipid bilayer composed of inner leaflet glycerophospholipids and outer leaflet lipooligosaccharides.

Glucose-Induced Biofilm Accessory Protein A (GbaA) Is a Monothiol-Dependent Electrophile Sensor.

is a commensal pathogen that has evolved to protect itself from unfavorable conditions by forming complex community structures termed biofilms. The regulation of the formation of these structures is multifactorial and in involves a number of transcriptional regulators. GbaA (glucose-induced biofilm accessory protein A) is a tetracycline repressor (TetR) family regulator that harbors two conserved Cys residues (C55 and C104) and impacts the regulation of formation of poly--acetylglucosamine-based biofilms in many methicillin-resistant (MRSA) strains.

The Response of to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation.

is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell surfaces. Here, we investigate the response of toward sodium sulfide (NaS), known to be associated with some biofilms at oxic/anoxic interfaces.

Histidine Utilization Is a Critical Determinant of Pathogenesis.

is a nosocomial pathogen capable of causing a range of diseases, including respiratory and urinary tract infections and bacteremia. Treatment options are limited due to the increasing rates of antibiotic resistance, underscoring the importance of identifying new targets for antimicrobial development. During infection, must acquire nutrients for replication and survival.

Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii.

Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance.

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites.

Zinc intoxication induces ferroptosis in A549 human lung cells.

Zinc (Zn) is an essential trace metal required for all forms of life, but is toxic at high concentrations. While the toxic effects of high levels of Zn are well documented, the mechanism of cell death appears to vary based on the study and concentration of Zn. Zn has been proposed as an anti-cancer treatment against non-small cell lung cancer (NSCLC).

The Innate Immune Protein S100A9 Protects from T-Helper Cell Type 2-mediated Allergic Airway Inflammation.

Calprotectin is a heterodimer of the proteins S100A8 and S100A9, and it is an abundant innate immune protein associated with inflammation. In humans, calprotectin transcription and protein abundance are associated with asthma and disease severity. However, mechanistic studies in experimental asthma models have been inconclusive, identifying both protective and pathogenic effects of calprotectin.

Cuts Both Ways: Proteases Modulate Virulence of Enterohemorrhagic .

Enterohemorrhagic (EHEC) is a major cause of foodborne gastrointestinal illness. EHEC uses a specialized type III secretion system (T3SS) to form attaching and effacing lesions in the colonic epithelium and outcompete commensal gut microbiota to cause disease. A recent report in (E.

Assessing Acinetobacter baumannii Virulence and Persistence in a Murine Model of Lung Infection.

Acinetobacter baumannii is a Gram-negative opportunistic pathogen and a leading cause of ventilator-associated pneumonia. Murine models of A. baumannii lung infection allow researchers to experimentally assess A.

An Integrated, High-Throughput Strategy for Multiomic Systems Level Analysis.

Proteomics, metabolomics, and transcriptomics generate comprehensive data sets, and current biocomputational capabilities allow their efficient integration for systems biology analysis. Published multiomics studies cover methodological advances as well as applications to biological questions. However, few studies have focused on the development of a high-throughput, unified sample preparation approach to complement high-throughput omic analytics.

Defining the interaction of the protease CpaA with its type II secretion chaperone CpaB and its contribution to virulence in species.

, , and are a frequent cause of multidrug-resistant, healthcare-associated infections. Our previous work demonstrated that M2 possesses a functional type II secretion system (T2SS) that is required for full virulence. Further, we identified the metallo-endopeptidase CpaA, which has been shown previously to cleave human Factor V and deregulate blood coagulation, as the most abundant type II secreted effector protein.

Hydrogen Sulfide and Reactive Sulfur Species Impact Proteome S-Sulfhydration and Global Virulence Regulation in Staphylococcus aureus.

Hydrogen sulfide (HS) is thought to protect bacteria from oxidative stress, but a comprehensive understanding of its function in bacteria is largely unexplored. In this study, we show that the human pathogen Staphylococcus aureus (S. aureus) harbors significant effector molecules of HS signaling, reactive sulfur species (RSS), as low molecular weight persulfides of bacillithiol, coenzyme A, and cysteine, and significant inorganic polysulfide species.

Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in .

is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (HS) and nitric oxide (NO·) protect from antibiotic stress synergistically, which we propose involves the intermediacy of nitroxyl (HNO). Here, we examine the effect of exogenous sulfide and HNO on the transcriptome and the formation of low-molecular-weight (LMW) thiol persulfides of bacillithiol, cysteine, and coenzyme A as representative of reactive sulfur species (RSS) in wild-type and Δ strains of .

Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action.

An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action.

Transition Metals and Virulence in Bacteria.

Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies.

Medically Relevant Acinetobacter Species Require a Type II Secretion System and Specific Membrane-Associated Chaperones for the Export of Multiple Substrates and Full Virulence.

Acinetobacter baumannii, A. nosocomialis, and A. pittii have recently emerged as opportunistic human pathogens capable of causing severe human disease; however, the molecular mechanisms employed by Acinetobacter to cause disease remain poorly understood.