Characteristics and genomic epidemiology of colistin-resistant Enterobacterales from farmers, swine, and hospitalized patients in Thailand, 2014-2017.

Background: Colistin is one of the last resort therapeutic options for treating carbapenemase-producing Enterobacterales, which are resistant to a broad range of beta-lactam antibiotics. However, the increased use of colistin in clinical and livestock farming settings in Thailand and China, has led to the inevitable emergence of colistin resistance. To better understand the rise of colistin-resistant strains in each of these settings, we characterized colistin-resistant Enterobacterales isolated from farmers, swine, and hospitalized patients in Thailand.

Advancing development of medical countermeasures: Incorporating COVID-19 lessons learned into future pandemic preparedness planning.

The COVID-19 pandemic profoundly disrupted, and, out of necessity, accelerated innovation of research and development of medical countermeasures to combat COVID-19. Although countermeasures were developed with unprecedented speed as a result of decades of long-term Federal investments in platform technologies and existing partnerships, the pandemic also revealed gaps in our preparedness and response capabilities that threaten our readiness posture. Challenges include limited federal funding that hinders sustainable development and manufacturing of, and equitable access to, medical countermeasures.

Imipenem/Relebactam Resistance in Clinical Isolates of Extensively Drug Resistant Pseudomonas aeruginosa: Inhibitor-Resistant β-Lactamases and Their Increasing Importance.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are a major clinical challenge. Many isolates are carbapenem resistant, which severely limits treatment options; thus, novel therapeutic combinations, such as imipenem-relebactam (IMI/REL), ceftazidime-avibactam (CAZ/AVI), ceftolozane-tazobactam (TOL/TAZO), and meropenem-vaborbactam (MEM/VAB) were developed. Here, we studied two extensively drug-resistant (XDR) P.

Assay for Assessing Mucin Binding to Bacteria and Bacterial Proteins.

, a Gram-negative bacterium and the causative agent of Legionnaires' disease, exports over 300 effector proteins/virulence factors, through its type II (T2SS) and type IV secretion systems (T4SS). One such T2SS virulence factor, ChiA, not only functions as a chitinase, but also as a novel mucinase, which we believe aids ChiA-dependent virulence during lung infection. Previously published protocols manipulated wild-type strain 130b and its mutant to express plasmid-encoded GFP.

AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

Objectives: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates.

Methods: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target.

Structure, Dynamics and Cellular Insight Into Novel Substrates of the Type II Secretion System.

is a Gram-negative bacterium that is able to replicate within a broad range of aquatic protozoan hosts. is also an opportunistic human pathogen that can infect macrophages and epithelia in the lung and lead to Legionnaires' disease. The type II secretion system is a key virulence factor of and is used to promote bacterial growth at low temperatures, regulate biofilm formation, modulate host responses to infection, facilitate bacterial penetration of mucin gels and is necessary for intracellular growth during the initial stages of infection.

Structure and functional analysis of the Legionella pneumophila chitinase ChiA reveals a novel mechanism of metal-dependent mucin degradation.

Chitinases are important enzymes that contribute to the generation of carbon and nitrogen from chitin, a long chain polymer of N-acetylglucosamine that is abundant in insects, fungi, invertebrates and fish. Although mammals do not produce chitin, chitinases have been identified in bacteria that are key virulence factors in severe respiratory, gastrointestinal and urinary diseases. However, it is unclear how these enzymes are able to carry out this dual function.

Complete Genome Sequence of Staphylococcus aureus Phage SA75, Isolated from Goat Feces.

Antibiotic-resistant is an opportunistic pathogen causing serious human infections worldwide. Here, we report the complete annotated genome of bacteriophage SA75, a member of the family which could be an alternative to traditional antibiotics for treating infections. We used a hybrid approach combining MinION and Illumina MiSeq sequencing, which yielded a 43,134-bp genome and 65 open reading frames.

Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice, but little is known about the microbial factors that are responsible for this process.

Type II Secretion Promotes Bacterial Growth within the -Containing Vacuole in Infected Amoebae.

It was previously determined that the type II secretion system (T2SS) promotes the ability of to grow in coculture with amoebae. Here, we discerned the stage of intracellular infection that is potentiated by comparing the wild-type and T2SS mutant legionellae for their capacity to parasitize Whereas the mutant behaved normally for entry into the host cells and subsequent evasion of degradative lysosomes, it was impaired in the ability to replicate, with that defect being first evident at approximately 9 h postentry. The replication defect was initially documented in three ways: by determining the numbers of CFU recovered from the lysates of the infected monolayers, by monitoring the levels of fluorescence associated with amoebal monolayers infected with green fluorescent protein (GFP)-expressing bacteria, and by utilizing flow cytometry to quantitate the amounts of GFP-expressing bacteria in individual amoebae.

Assessing the impact, genomics and evolution of type II secretion across a large, medically important genus: the Legionella type II secretion paradigm.

The type II secretion system (T2SS) plays a major role in promoting bacterial survival in the environment and in human hosts. One of the best characterized T2SS is that of Legionella pneumophila, the agent of Legionnaires' disease. Secreting at least 25 proteins, including degradative enzymes, eukaryotic-like proteins and novel effectors, this T2SS contributes to the ability of L.

Closed Genome Sequences of Clinical Neisseria gonorrhoeae Strains Obtained from Combined Oxford Nanopore and Illumina Sequencing.

Neisseria gonorrhoeae is the etiological agent of gonorrhea, the second most common notifiable disease in the United States. Here, we used a hybrid approach combining Oxford Nanopore Technologies MinION and Illumina MiSeq sequencing data to obtain closed genome sequences of nine clinical N. gonorrhoeae isolates.

Type II Secretion-Dependent Aminopeptidase LapA and Acyltransferase PlaC Are Redundant for Nutrient Acquisition during Intracellular Infection of Amoebas.

genes encoding LapA, LapB, and PlaC were identified as the most highly upregulated type II secretion (T2S) genes during infection of , although these genes had been considered dispensable on the basis of the behavior of mutants lacking either and or A mutant showed even higher levels of and transcripts, and a mutant showed heightening of mRNA levels, suggesting that the role of the LapA/B aminopeptidase is compensatory with respect to that of the PlaC acyltransferase. Hence, we made double mutants and found that mutants have an ~50-fold defect during infection of These data revealed, for the first time, the importance of LapA in any sort of infection; thus, we purified LapA and defined its crystal structure, activation by another T2S-dependent protease (ProA), and broad substrate specificity. When the amoebal infection medium was supplemented with amino acids, the defect of the mutant was reversed, implying that LapA generates amino acids for nutrition.

Type II Secretion Substrates of Translocate Out of the Pathogen-Occupied Vacuole via a Semipermeable Membrane.

replicates in macrophages in a host-derived phagosome, termed the containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM).

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond.

Type II secretion (T2S) is one means by which Gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. Based upon recent genome sequencing, it is clear that T2S is largely restricted to the , occurring in many, but not all, genera in the , , , and classes. Prominent human and/or animal pathogens that express a T2S system(s) include , , , , , , , , , and T2S-expressing plant pathogens include , , , , , , and T2S also occurs in nonpathogenic bacteria, facilitating symbioses, among other things.

Type II Secretion Is Necessary for Optimal Association of the Legionella-Containing Vacuole with Macrophage Rab1B but Enhances Intracellular Replication Mainly by Rab1B-Independent Mechanisms.

Previously, we documented that type II secretion (T2S) promotes intracellular infection of macrophages by Legionella pneumophila In the present study, we identified infection events that are modulated by T2S by comparing the behaviors of wild-type and T2S mutant bacteria in murine bone marrow-derived macrophages and human U937 cells. Although the two strains behaved similarly for entry into the host cells and evasion of lysosomal fusion, the mutant was impaired in the ability to initiate replication between 4 and 8 h postentry and to grow to large numbers in the Legionella-containing vacuole (LCV), as evident at 12 h. At 4 h postinoculation, mutant LCVs had a significantly reduced association with Rab1B, a host GTPase that facilitates the tethering of endoplasmic reticulum (ER)-derived vesicles to LCVs.

The stigma of mental illness in the labor market.

Mental illness labels are accompanied by devaluation and discrimination. We extend research on reactions to mental illness by utilizing a field experiment (N = 635) to test effects of mental illness labels on labor market discrimination. This study involved sending fictitious applications to job listings, some applications indicating a history of mental illness and some indicating a history of physical injury.

Stenotrophomonas maltophilia encodes a type II protein secretion system that promotes detrimental effects on lung epithelial cells.

The Gram-negative bacterium Stenotrophomonas maltophilia is increasingly identified as a multidrug-resistant pathogen, being associated with pneumonia, among other infections. Despite this increasing clinical problem, the genetic and molecular basis of S. maltophilia virulence is quite minimally defined.

p53 and mitochondrial DNA: their role in mitochondrial homeostasis and toxicity of antiretrovirals.

The roles and actions of the tumor suppressor protein p53 have been extensively studied with regard to nuclear events, including transcription and DNA damage repair. However, the direct roles of p53 in mitochondrial DNA (mtDNA) replication and function are less well understood. Studies herein used a mitochondrial-targeted p53 (MTS-p53) to determine its effects on both mtDNA abundance and mitochondrial function.