mSphere® An ASM Access® Publication

Cyclic di-AMP (c-di-AMP) is an essential bacterial second messenger that coordinates multiple cellular processes and is closely linked to central physiology in many bacteria. In Staphylococcus aureus, both depletion and excessive accumulation of c-di-AMP impair bacterial fitness, indicating that this signaling pathway must be tightly regulated. Recent studies have identified c-di-AMP receptor proteins in S. aureus, revealing how c-di-AMP maintains osmotic balance through ion transport and...

Organoids provide a useful model system to study interactions between gut microbes and the activity of host tissues, including gastrointestinal (GI) barrier function. However, most organoid models have limited capacity to mimic the physiological hypoxia experienced by the colonic epithelium in vivo. While oxygen is required to support respiration in the host cells, many gut microbes are anaerobes that require anoxic conditions to grow. Using an innovative anaerobe co-culture system that...

A safe, effective, and affordable vaccine that can prevent Shigella-induced diarrhea could have a significant impact on reducing morbidity and mortality in populations at risk. WRSS1, a live attenuated Shigella sonnei vaccine candidate, was well tolerated and immunogenic in adult Thai volunteers, achieving 40% efficacy against wild-type (WT) S. sonnei. We performed an in-depth analysis of mucosal and systemic antibodies in these individuals following WRSS1 vaccination and S. sonnei challenge,...

The incidence of disseminated gonococcal infection (DGI) has remained low since the advent of antibiotics; however, a recent surge in DGI has inexplicably emerged during the past decade. In an effort to understand whether Neisseria gonorrhoeae that cause disseminated disease can be differentiated from non-invasive strains, we have performed a phenotypic and genotypic analysis on a selection of isolates obtained from invasive and uncomplicated infections in Canada. The increase in DGI was...

Satoshi Kimura works in the field of RNA modification. In this mSphere of Influence article, he reflects on how the paper "Efficient and quantitative high-throughput tRNA sequencing" by G. Zheng, Y. Qin, W. C. Clark, Q. Dai, et al. (Nat. Methods 12:835-837, 2015, https://doi.org/10.1038/nmeth.3478) has impacted him by demonstrating that deep sequencing technology is harnessed to profile tRNA modifications.

Antimicrobial resistance (AMR) is increasingly recognized as a One Health challenge driven by the continuous exchange of resistant bacteria and resistance determinants across human, animal, and environmental sectors. While genomic surveillance has substantially improved detection of antimicrobial resistance genes (ARGs), most monitoring frameworks remain gene- or isolate-centric, limiting insight into the mechanisms that govern resistance transmission and persistence. Recent evidence indicates...

Hundreds of ribotypes of the gastrointestinal pathogen Clostridioides difficile have emerged over the last three decades, yet the factors driving their emergence are poorly understood. Recently, there has been an increase in infections caused by PCR ribotype 023 (RT023) strains in Europe. We profiled the growth of seven RT023 strains in 190 unique carbon sources and found they were able to grow in xylitol, a sugar alcohol used as a food additive in humans and animals. Other ribotypes of C....

Looking back over the past 50 years, staphylococcal research has evolved from a relatively narrow niche into a broad, interdisciplinary field encompassing genetics, genomics, bioinformatics, host-bacterium interactions, immunity, microbial ecology, the microbiota, and commensalism. My career progressed in parallel with these research developments. Much of what contributed to my success was the ability to recognize emerging questions early on, to combine classical microbiology with new...

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Oxygen minimum zones (OMZs) are expanding in the global ocean. Declining oxygen can alter microbial processes that regulate carbon, nitrogen, and sulfur cycling, including pathways with the potential to produce nitrous oxide (N₂O), a potent greenhouse gas. Yet, we lack a full understanding of how microbial communities respond to declining oxygen in some globally important OMZs. This is particularly true for the understudied northern Benguela Upwelling System (nBUS), an important source of marine...

We studied the effects of a combined water, sanitation, handwashing, and nutritional supplementation (WSH + N) intervention on Shigella/EIEC IgG immune development among Bangladeshi children enrolled in a cluster-randomized trial. We used a bacterial display assay to measure IgG-specific binding to Shigella/EIEC Ipa proteins (IpaA, IpaB, IpaC, IpaD, and IpaH) from a substudy of 120 children (60 intervention, 60 control) at median ages 3, 14, and 28 months. We found that the WSH + N intervention...

Plasmodium spp. have different modes of cell division from most eukaryotes. Little is known about how these are controlled, and cell cycle checkpoints are particularly poorly characterized. However, parasites can arrest their cell cycle when treated with the frontline antimalarial drug artemisinin, and artemisinin-resistant parasites can modulate their cell cycle progression, so it is important to understand these aspects of Plasmodium biology. Here, we show that P. falciparum displays hallmarks...

Nearly 4 billion people worldwide reside in dengue virus (DENV) endemic areas. Primary dengue infection generates both type-specific and cross-reactive immunity. While serotype-specific immunity provides long-term protection against homologous virus challenge, cross-reactive immunity is short-lived and, upon subsequent heterotypic exposure, can increase the risk of severe clinical outcomes. Therefore, it is critical to measure type-specific immunity. The current resource-intensive and...

Extraintestinal pathogenic Escherichia coli (ExPEC) frequently produce Group 2 or 3 capsules that enhance virulence, yet genetic regulation and specific roles of Group 3 capsules remain poorly understood. Here, we demonstrate that the K96 Group 3 capsule in ExPEC strain M12 confers resistance to human serum complement. Using genetic screens, we identified phase-variable mutations in kpsC and essential roles for transcriptional regulators OxyR and RfaH in activating capsule synthesis via a...

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in...