Analysis of Mutations in Dihydropteroate Synthase and Dihydropteroate Reductase Genes Among Non-HIV Patients in China.

Purpose: pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of in non-HIV patients in China, providing a reference for drug usage.

A temperature-induced metabolic shift in the emerging human pathogen .

Unlabelled: is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic adaptations have been proposed to facilitate the survival of this pathogen at higher temperatures, yet the biological mechanisms underlying these are poorly understood.

The Pvc15 ATPase selectively associates effector proteins with the virulence cassette.

The virulence cassette (PVC) is an extracellular contractile injection system. In the producing bacterium, N-terminal signal peptides enable effector 'payloads' to be loaded into the PVC's hollow tube-facilitated by the 'ATPases associated with diverse cellular activities' (AAA) ATPase, Pvc15-ready for injection of the toxin or virulence factor into eukaryotic cytosols. Pvc15's function and its interaction with the signal peptide were unclear.

Insight into the emerging insect to human pathogen revealing geographic differences in immune cell tropism.

Background: is a species of the insect pathogenic genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells.

Genome wide analysis revealed conserved domains involved in the effector discrimination of bacterial type VI secretion system.

Type VI secretion systems (T6SSs) deliver effectors into target cells. Besides structural and effector proteins, many other proteins, such as adaptors, co-effectors and accessory proteins, are involved in this process. MIX domains can assist in the delivery of T6SS effectors when encoded as a stand-alone gene or fused at the N-terminal of the effector.

The influence of extrachromosomal elements in the anthrax "cross-over" strain G9241.

G9241 was isolated from a welder who survived a pulmonary anthrax-like disease. Strain G9241 carries two virulence plasmids, pBCX01 and pBC210, as well as an extrachromosomal prophage, pBFH_1. pBCX01 has 99.

From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the "cross-over" strain G9241.

G9241 was isolated from a Louisiana welder suffering from an anthrax-like infection. The organism carries two transcriptional regulators that have previously been proposed to be incompatible with each other in : the pleiotropic transcriptional regulator PlcR found in most members of the group but truncated in all isolates, and the anthrax toxin regulator AtxA found in all strains and a few strains. Here we report cytotoxic and hemolytic activity of cell free G9241 culture supernatants cultured at 25°C to various eukaryotic cells.

Establish an allele-specific real-time PCR for Leishmania species identification.

Background: Leishmaniasis is a serious neglected tropical disease that may lead to life-threatening outcome, which species are closely related to clinical diagnosis and patient management. The current Leishmania species determination method is not appropriate for clinical application. New Leishmania species identification tool is needed using clinical samples directly without isolation and cultivation of parasites.

Detection of Pneumocystis jirovecii and Toxoplasma gondii in patients with lung infections by a duplex qPCR assay.

Pneumocystis pneumonia (PCP) and pulmonary toxoplasmosis (PT) are caused by Pneumocystis jirovecii and Toxoplasma gondii. The clinical symptoms and imaging of PCP and PT are indistinguishable. A duplex qPCR was developed to differentiate between these two pathogens.

A new family of globally distributed lytic roseophages with unusual deoxythymidine to deoxyuridine substitution.

Marine bacterial viruses (bacteriophages) are abundant biological entities that are vital for shaping microbial diversity, impacting marine ecosystem function, and driving host evolution. The marine roseobacter clade (MRC) is a ubiquitous group of heterotrophic bacteria that are important in the elemental cycling of various nitrogen, sulfur, carbon, and phosphorus compounds. Bacteriophages infecting MRC (roseophages) have thus attracted much attention and more than 30 roseophages have been isolated, the majority of which belong to the N4-like group (Podoviridae family) or the Chi-like group (Siphoviridae family), although ssDNA-containing roseophages are also known.

Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins.

Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits.

N-Glycans and sulfated glycosaminoglycans contribute to the action of diverse Tc toxins on mammalian cells.

Tc toxin is an exotoxin composed of three subunits named TcA, TcB and TcC. Structural analysis revealed that TcA can form homopentamer that mediates the cellular recognition and delivery processes, thus contributing to the host tropism of Tc toxin. N-glycans and heparan sulfates have been shown to act as receptors for several Tc toxins.

Application of Quantitative PCR in the Diagnosis and Evaluating Treatment Efficacy of Leishmaniasis.

Leishmaniasis is still a serious neglected tropical disease that may cause death in infected individuals. At present, the clinical diagnosis and treatment monitoring still rely on parasitological culture and microscopy that needs experienced technicians. The low sensitivity and inconvenience of microscopic examination could cause misdiagnosis and relapse of leishmaniasis.

Temperature Restriction in Entomopathogenic Bacteria.

Temperature plays an important role in bacteria-host interactions and can be a determining factor for host switching. In this study we sought to investigate the reasons behind growth temperature restriction in the entomopathogenic enterobacterium . has a complex dual symbiotic and pathogenic life cycle.

Metallohelices that kill Gram-negative pathogens using intracellular antimicrobial peptide pathways.

A range of new water-compatible optically pure metallohelices - made by self-assembly of simple non-peptidic organic components around Fe ions - exhibit similar architecture to some natural cationic antimicrobial peptides (CAMPs) and are found to have high, structure-dependent activity against bacteria, including clinically problematic Gram-negative pathogens. A key compound is shown to freely enter rapidly dividing cells without significant membrane disruption, and localise in distinct foci near the poles. Several related observations of CAMP-like mechanisms are made biophysical measurements, whole genome sequencing of tolerance mutants and transcriptomic analysis.

The virulence cassettes deliver protein effectors directly into target eukaryotic cells.

is a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, the Virulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins.

Iso-propyl stilbene: a life cycle signal?

Members of the Gram-negative bacterial genus Photorhabdus are all highly insect pathogenic and exist in an obligate symbiosis with the entomopathogenic nematode worm Heterorhabditis. All members of the genus produce the small-molecule 3,5-dihydroxy-4-isopropyl-trans-stilbene (IPS) as part of their secondary metabolism. IPS is a multi-potent compound that has antimicrobial, antifungal, immunomodulatory and anti-cancer activities and also plays an important role in symbiosis with the nematode.

Coping with Environmental Eukaryotes; Identification of Genes during the Interaction with Alternative Hosts or Predators.

Understanding the molecular mechanisms underpinning the ecological success of plant pathogens is critical to develop strategies for controlling diseases and protecting crops. Recent observations have shown that plant pathogenic bacteria, particularly , exist in a range of natural environments away from their natural plant host e.g.

The Pseudomonas aeruginosa Type VI Secretion PGAP1-like Effector Induces Host Autophagy by Activating Endoplasmic Reticulum Stress.

Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells. Here, we report a detailed investigation of a P.

Anticancer metallohelices: nanomolar potency and high selectivity.

A range of new helicate-like architectures have been prepared highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [FeL]Cl·HO (L = various bidentate ditopic ligands NN-NN) show very good water solubility and stability. Their activity against a range of cancer cell lines is structure-dependent and gives IC values as low as 40 nM.

From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates.

A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells.

Widely found in animal and plant-associated proteobacteria, type VI secretion systems (T6SSs) are potentially capable of facilitating diverse interactions with eukaryotes and/or other bacteria. Pseudomonas aeruginosa encodes three distinct T6SS haemolysin coregulated protein (Hcp) secretion islands (H1, H2, and H3-T6SS), each involved in different aspects of the bacterium's interaction with other organisms. Here we describe the characterization of a P.

Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds.

There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells.

Oxacillin alters the toxin expression profile of community-associated methicillin-resistant Staphylococcus aureus.

The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a growing cause for concern. These strains are more virulent than health care-associated MRSA (HA-MRSA) due to higher levels of toxin expression. In a previous study, we showed that the high-level expression of PBP2a, the alternative penicillin binding protein encoded by the mecA gene on type II staphylococcal cassette chromosome mec (SCCmec) elements, reduced toxicity by interfering with the Agr quorum sensing system.