Characterization of outer membrane vesicles released by clinical isolates of Neisseria gonorrhoeae.

The sexually transmitted pathogen Neisseria gonorrhoeae releases membrane vesicles including outer membrane vesicles (OMVs) during infections. OMVs traffic outer membrane molecules, such as the porin PorB and lipo-oligosaccharide (LOS), into host innate immune cells, eliciting programmed cell death pathways, and inflammation. Little is known, however, about the proteome and LOS content of OMVs released by clinical strains isolated from different infection sites, and whether these vesicles similarly activate immune responses.

Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages.

Global spread of multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages underscores the need for new therapeutic strategies. Here we show that many S. epidermidis isolates belonging to these lineages display cryptic susceptibility to penicillin/β-lactamase inhibitor combinations under in vitro conditions, despite carrying the methicillin resistance gene mecA.

Genomic surveillance for antimicrobial resistance - a One Health perspective.

Antimicrobial resistance (AMR) - the ability of microorganisms to adapt and survive under diverse chemical selection pressures - is influenced by complex interactions between humans, companion and food-producing animals, wildlife, insects and the environment. To understand and manage the threat posed to health (human, animal, plant and environmental) and security (food and water security and biosecurity), a multifaceted 'One Health' approach to AMR surveillance is required. Genomic technologies have enabled monitoring of the mobilization, persistence and abundance of AMR genes and mutations within and between microbial populations.

A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteremia.

Outcomes of severe bacterial infections are determined by the interplay between host, pathogen, and treatments. While human genomics has provided insights into host factors impacting Staphylococcus aureus infections, comparatively little is known about S. aureus genotypes and disease severity.

Case Commentary: The hidden side of oxacillin resistance in .

Acquisition of PBP2a (encoded by the gene) is the key resistance mechanism to β-lactams in . The gene can be easily detected by PCR assays; however, these tools will miss c-independent oxacillin resistance. This phenotype is mediated by mutations in cell wall metabolism genes that can be acquired during persistent infections under prolonged antibiotic exposure.

Reducing unnecessary testing on sputum specimens from patients with cystic fibrosis: pathology stewardship in microbiology.

Chronic respiratory tract infection by Pseudomonas aeruginosa is the hallmark of established lung disease in patients with cystic fibrosis (CF). Antibiotic therapy can usually only suppress but not eradicate infection. In recent years, pulmonary infection with non-tuberculous Mycobacteria (NTM) species has also been increasing.

Development of virus-like particles with inbuilt immunostimulatory properties as vaccine candidates.

The development of virus-like particle (VLP) based vaccines for human papillomavirus, hepatitis B and hepatitis E viruses represented a breakthrough in vaccine development. However, for dengue and COVID-19, technical complications, such as an incomplete understanding of the requirements for protective immunity, but also limitations in processes to manufacture VLP vaccines for enveloped viruses to large scale, have hampered VLP vaccine development. Selecting the right adjuvant is also an important consideration to ensure that a VLP vaccine induces protective antibody and T cell responses.

A Clinically Selected Staphylococcus aureus Mutant Survives Daptomycin Treatment by Reducing Binding of the Antibiotic and Adapting a Rod-Shaped Morphology.

Daptomycin is a last-resort antibiotic used for the treatment of infections caused by Gram-positive antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Treatment failure is commonly linked to accumulation of point mutations; however, the contribution of single mutations to resistance and the mechanisms underlying resistance remain incompletely understood. Here, we show that a single nucleotide polymorphism (SNP) selected during daptomycin therapy inactivates the highly conserved ClpP protease and is causing reduced susceptibility of MRSA to daptomycin, vancomycin, and β-lactam antibiotics as well as decreased expression of virulence factors.

Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 and/or CTLA-4.

Introduction: HIV-1 persists in resting CD4 T-cells despite antiretroviral therapy (ART). Determining the cell surface markers that enrich for genetically-intact HIV-1 genomes is vital in developing targeted curative strategies. Previous studies have found that HIV-1 proviral DNA is enriched in CD4 T-cells expressing the immune checkpoint markers programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocyte associated protein-4 (CTLA-4).

All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: Results of GWAS and experimental animal studies.

Objectives: We aimed at determining whether specific S. aureus strains cause infective endocarditis (IE) in the course of Staphylococcus aureus bacteraemia (SAB).

Methods: A genome-wide association study (GWAS) including 924 S.

Niche-specific genome degradation and convergent evolution shaping adaptation during severe infections.

During severe infections, moves from its colonising sites to blood and tissues and is exposed to new selective pressures, thus, potentially driving adaptive evolution. Previous studies have shown the key role of the locus in pathoadaptation; however, a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2590 .

Reprogramming of Cell Death Pathways by Bacterial Effectors as a Widespread Virulence Strategy.

The modulation of programmed cell death (PCD) processes during bacterial infections is an evolving arms race between pathogens and their hosts. The initiation of apoptosis, necroptosis, and pyroptosis pathways are essential to immunity against many intracellular and extracellular bacteria. These cellular self-destructive mechanisms are used by the infected host to restrict and eliminate bacterial pathogens.

ICOS-play: dressing T cells for residency.

Efficient generation of tissue-resident memory T (T) cells is essential for long-lived immune protection in barrier tissues. Peng et al. now show that the costimulatory molecule ICOS enhances CD8 T cell lodgment by promoting early tissue retention.

Viral, inflammatory, and reservoir characteristics of posttreatment controllers.

Purpose Of Review: To provide an overview of studies to date that have identified posttreatment controllers (PTCs) and to explore current evidence around clinical characteristics, immune effector function, and inflammatory and viral reservoir characteristics that may underlie the control mechanism.

Recent Findings: PTCs are broadly defined as individuals capable of maintaining control of HIV replication after cessation of antiretroviral therapy (ART). While starting ART early after HIV infection is associated with PTC, genetic disposition or CD8+ T-cell function do not appear to explain this phenomenon, but these features have not been exhaustively analyzed in PTCs.

Spatial and Temporal Epidemiology of Infectious Syphilis in Victoria, Australia, 2015-2018.

This analysis of notified syphilis cases in Victoria, Australia between 2015 and 2018 shows that the syphilis epidemic in Victoria has become more generalized, with increases among heterosexual men and women residing in outer Melbourne suburbs-areas that differ from those of gay men.

Clinical relevance of topical antibiotic use in co-selecting for multidrug-resistant : Insights from and models.

Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin resistant in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in following exposure to FA or mupirocin.

Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus.

Antistaphylococcal penicillins such as oxacillin are the key antibiotics in the treatment of invasive methicillin-susceptible (MSSA) infections; however, gene-independent resistance adaptation can cause treatment failure. Despite its clinical relevance, the basis of this phenomenon remains poorly understood. Here, we investigated the genomic adaptation to oxacillin at an unprecedented scale using a large collection of 503 clinical -negative isolates and 30 -adapted isolates from independent oxacillin exposures.

induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes.

is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system.

Gonorrhoea: tackling the global epidemic in the era of rising antimicrobial resistance.

This Special Issue of Sexual Health aims to collate the latest evidence base focussed on understanding the current epidemic and transmission of gonorrhoea, choice of treatment, molecular epidemiology application, concerns about antimicrobial resistance and alternative prevention and control for gonorrhoea.

Immunity to hepatitis A among men who have sex with men attending a large sexual health clinic in Melbourne, Australia, 2012-2018.

Background: Outbreaks of hepatitis A are being reported more commonly among men who have sex with men (MSM) globally. Australia has also reported a sharp increase in the number of cases of hepatitis A in 2017. This study aimed to determine the level of immunity to hepatitis A among MSM attending a large urban sexual health clinic in Victoria in the lead up to recent outbreak.

Mining the Methylome Reveals Extensive Diversity in Staphylococcus epidermidis Restriction Modification.

is a significant opportunistic pathogen of humans. Molecular studies in this species have been hampered by the presence of restriction-modification (RM) systems that limit introduction of foreign DNA. Here, we establish the complete genomes and methylomes for seven clinically significant, genetically diverse isolates and perform the first systematic genomic analyses of the type I RM systems within both and Our analyses revealed marked differences in the gene arrangement, chromosomal location, and movement of type I RM systems between the two species.