mBio® An ASM Access® Publication

The major route of COVID-19 vaccination currently is via intramuscular injection. Data from clinical trials and real-world studies have demonstrated its effectiveness in preventing severe illness and death caused by SARS-CoV-2 infection. However, its protective efficacy against SARS-CoV-2 infection and transmission in situ remains relatively low. Given that SARS-CoV-2, especially the Omicron variant and its sub-variants, primarily infects and replicates in the human upper respiratory tract,...

Mycobacterium tuberculosis (Mtb) remodels host cell functions to support its persistence within macrophages. While infected cells have been extensively studied, the responses of uninfected bystander macrophages in the same microenvironment remain poorly understood. Here, we demonstrate that Mtb infection triggers broad epigenetic and transcriptional reprogramming in bystander macrophages, predominantly via interleukin-1β-dependent nuclear factor-κB signaling from infected cells. These bystander...

The increasing prevalence of triazole resistance among Aspergillus fumigatus clinical isolates threatens the efficacy of this front-line treatment, highlighting the urgent need for novel therapeutic targets. In this study, we characterized three putative lanosterol synthase (also known as oxidosqualene cyclase) paralogs and identified Erg7A as the dominant enzyme. Although erg7B provided functional redundancy when overexpressed, deletion of erg7A alone created a significant ergosterol...

Quorum sensing (QS) enables microorganisms-including bacteria, eukaryotes, and viruses-to coordinate collective behaviors in response to population density. Despite their ecological and evolutionary significance, QS mechanisms in Archaea remain poorly characterized. The halophilic archaeon Haloferax volcanii provides a model for archaeal QS, transitioning from motile rods to non-motile disks in a density-dependent response to a secreted disk-forming signal (DFS). To identify components of the...

Plasmodium remodels the host liver cell as an obligatory step in malaria infection. Although several host proteins are recruited to the parasitophorous vacuole membrane (PVM) after invasion, the mechanisms underlying this acquisition remain unknown. Here, we validated the upregulation and recruitment of the host protein CGA during liver stage Plasmodium berghei infection. We then depleted a panel of host trafficking proteins to investigate their role in CGA recruitment to the P. berghei PVM....

The bacterial second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) governs the transition from motile to sessile lifestyle by suppressing flagellar motility and promoting the synthesis of the extracellular biofilm matrix. In Escherichia coli, a main contributor to the global c-di-GMP pool is the diguanylate cyclase DgcE. It was recently shown that DgcE is activated by physical interaction with the dynamin-like GTPase RdcA and its accessory protein RdcB, but molecular...

Chlamydia trachomatis is a gram-negative obligate intracellular pathogenic bacterium that is a leading cause of sexually transmitted and ocular infections. Pathogenic Chlamydia species have a distinct, essential, and tightly controlled biphasic developmental cycle. The non-replicative elementary body (EB) infects a cell and undergoes primary differentiation to the non-infectious reticulate body (RB), which undergoes multiple rounds of division. The shift from the replicative RB form to its...

Candida albicans causes infections of the central nervous system in premature infants and people with primary immune deficiencies affecting the innate immune system. Compared to infections in other organs, the pathogenesis and host responses to C. albicans brain infections are understudied. However, the CARD9/NLRP3/interleukin 1 (IL-1) axis has been shown to play a central role in protecting the brain from C. albicans through the recruitment of neutrophils. In addition, Ece1/candidalysin is a...

We previously identified isoleucine-proline-isoleucine (IPI) as a small molecule associated with extracellular vesicles (EVs) in Cryptococcus. The administration of IPI in vivo resulted in the control of experimental cryptococcal infection through mechanisms that remain unknown. IPI is an inhibitor of dipeptidyl peptidase 4 (Dpp4), an enzyme that regulates insulin and glucose homeostasis in mammals and may also influence pathogenic processes in fungi. Based on these observations, we investigated...

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Several widespread mechanisms enable cellular communication and coordinate the behavior of bacterial populations. The modules responsible for cellular communication are often found in matching pairs: an enzyme that synthesizes a signal molecule and a specific receptor that decodes it. A notable exception is Escherichia coli SdiA, a homolog of known N-acyl-homoserine lactone (AHL) receptors, for which no corresponding AHL synthase exists. SdiA is an orphan receptor that enables cross-talk by...

Shewanella oneidensis MR-1 is a model electroactive bacterium whose extracellular electron transfer (EET) pathway includes a sequential network of c-type cytochromes that span the inner membrane, periplasm, and outer membrane. While electrochemical studies have revealed the critical role of outer-membrane cytochromes in mediating both outward EET from cells to external surfaces and lateral biofilm conduction across cells, the specific functional role of periplasmic cytochromes in these processes...

Bacterial outer membrane vesicles (OMVs) contribute to virulence, competition, immune avoidance, and communication. This has led to great interest in how they are formed. To date, investigation has focused almost exclusively on what controls the initiation of OMV biogenesis. Regardless of the mechanism of initiation, all species face a similar challenge before an OMV can be released: how does the outer membrane (OM) detach from the underlying peptidoglycan (PG) in regions that will ultimately...

Conjugation machines constitute a large subfamily of the bacterial type IV secretion systems (T4SSs). In the absence of recipient cell contact, conjugation machines of gram-negative bacteria produce conjugative pili by extracting pilin subunits from an inner membrane (IM) pool. Upon pilus-mediated or direct contact with a target cell, conjugation systems transition to the recruitment of a cognate mobile element for intercellular DNA transfer. T4SS subunit requirements for pilus assembly and...

Reactive oxygen species (ROS) act both as cytotoxic agents and essential signaling molecules. In the nematode-trapping fungus Arthrobotrys flagrans, we investigated how ROS coordinate the development and function of adhesive trapping networks used to capture Caenorhabditis elegans. We demonstrate a distinct functional specialization between the two NADPH oxidases NoxA and NoxB, which are both activated by the regulatory subunit NoxR. The NoxB-NoxR complex was specifically active in trap cells,...