mSphere® An ASM Access® Publication

Trypanosoma cruzi, the etiologic agent of Chagas disease, alternates between replicative epimastigotes and amastigotes and non-dividing, mammal-infective metacyclic and bloodstream trypomastigotes. Protein phosphorylation is a major regulatory mechanism in trypanosomatids, whose kinomes reveal an expanded family of NIMA-related kinases (NEKs). Here, we investigated the role of T. cruzi RDK2 (repressor of differentiation kinase 2), a conserved NEK that carries a C-terminal pleckstrin homology...

Klebsiella pneumoniae and related species are a common cause of healthcare-associated infections. The gut is a major Klebsiella reservoir, and gut colonization is a risk factor for developing an extraintestinal Klebsiella infection. Patients can be colonized by multiple Klebsiella strains or even species in the gut simultaneously, and there is high concordance between the gut-colonizing and infection-causing strains. The detection and characterization of colonizing strains is critical for a...

Extracellular vesicles (EVs) are nano-sized lipid bilayer structures released by diverse cell types. For pathogenic fungi, EVs play critical roles by modulating immune responses and influencing disease progression. Previously, we demonstrated that vaccination with EVs from Candida albicans promoted protection in immunosuppressed mice subsequently infected with lethal doses of this organism. However, the impact of EVs in the presence of fungi is poorly investigated in vivo. Here, we demonstrated...

Marine diazotrophic cyanobacteria play a crucial role in oceanic nitrogen cycling, supporting primary production and ecosystem balance. Crocosphaera watsonii WH8501 exemplifies this capability by temporally separating photosynthesis and diazotrophy. To investigate the regulatory mechanisms underlying this process, we employed mass spectrometry-based proteomics in a high-resolution diel culturing experiment, revealing tightly coordinated protein abundance patterns. Unsupervised clustering of diel...

Pediatric infections with highly resistant Klebsiella pneumoniae (HR-Kp) disproportionately affect low-income countries where childhood malnutrition is prevalent. Malnutrition is an identified risk factor for infection with HR-Kp and other antimicrobial-resistant Enterobacterales, but the mechanistic underpinnings of this link and independence from other common exposures, like antibiotics, in children are unclear. Using a murine model of pediatric malnutrition, we found that mice fed a...

Peromyscus leucopus (P. leucopus) is an important reservoir host for several zoonoses, including Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. However, the immunoglobulin germline repertoire underlying antibody responses in this reservoir host remains poorly defined. In this study, we characterized the immunoglobulin variable genes of P. leucopus and identified 12 IGHV, 12 IGKV, and 3 IGLV gene families comprising 129, 87, and 12 genes, respectively. These genes...

People living with HIV (PLWH) have a higher risk of developing other diseases, such as bacterial pneumonia. Pseudomonas aeruginosa is a common cause of pneumonia in humans. The most virulent strains produce ExoU, which is a key effector of P. aeruginosa cytotoxicity. Upon injection into the target cell cytosol by the type III secretion system (T3SS), ExoU binds to PI(4,5)P(2) on the inner leaflet of the plasma membrane. ExoU phospholipase activity then induces a loss of plasma membrane...

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Urban public transport systems, particularly metro networks, serve as key hubs for microbial transmission, yet the urban microbiome in densely populated regions like India remains poorly characterized. Understanding these environments is crucial for public health, especially in light of the COVID-19 pandemic and growing concerns about antimicrobial resistance (AMR). This study is the first of its kind to investigate the microbial communities and the presence of AMR genes in the Chennai Metro...

Diffusible signal factors (DSFs) are a gammaproteobacterial family of quorum-sensing signals that mediate the transition between sessile and planktonic lifestyles. In addition to coordinating behavior within producing species, DSFs can be sensed by surrounding organisms, enabling interspecies "eavesdropping." Several enteric pathogens that do not produce DSFs use these environmental signals to modulate their virulence, allowing them to conserve energy when expression of pathogenesis genes is not...

Colistin (COL) serves as a last-line therapeutic agent against multidrug-resistant gram-negative bacteria (GNB) infections. Nevertheless, widespread clinical use of COL has led to severe bacterial resistance. The anthelmintic drug niclosamide (NIC) has been shown to enhance the activity of COL in combination therapy. Despite this synergistic advantage, the two compounds possess distinct physicochemical and pharmacokinetic properties. To enable simultaneous delivery of both drugs to the target...

Agrobacterium fabrum infects a wide range of plants, resulting in significant economic losses. In the rhizosphere, the bacterium is exposed to several stressors, including compounds secreted from other bacteria, fungi, or plants. A. fabrum encodes the efflux pump PecM for which the substrate is 4-hydroxybenzaldehyde, a compound that is both present in plant exudates and generated by bacteria during degradation of aromatic compounds. As an aromatic aldehyde, 4-hydroxybenzaldehyde is a chemically...

Prototheca, a genus of unpigmented yeast-like microscopic algae, is an emerging pathogen of humans and animals. Treatment of Prototheca infections is often unsuccessful because the unusual algal biology of these pathogens limits the availability of effective therapeutics. Here, we screened the Pandemic Response Box, a library of 400 compounds with potential anti-infective activity that are either clinically approved or in preclinical development, and identified five promising compounds with...

Brady Spencer is a bacteriologist studying host-pathogen-microbiota interactions. In this mSphere of Influence article, she reflects on how two studies from Scott Hultgren's laboratory on mucosal imprinting following Escherichia coli bladder infection (V. P. O'Brien, T. J. Hannan, L. Yu, J. Livny, et al., Nat Microbiol 2:16196, 2016, http://dx.doi.org/10.1038/nmicrobiol.2016.196; S. K. Russell, J. K. Harrison, B. S. Olson, H. J. Lee, et al., Nat Microbiol 8:875-888, 2023,...

Transmission of respiratory pathogens depends on their ability to remain viable in drying respiratory droplets, yet the physicochemical drivers of bacterial inactivation during droplet evaporation remain poorly quantified. This study combines controlled droplet experiments with physicochemical modeling to investigate how osmotic pressure dynamics influence bacterial survival. Using Escherichia coli and Staphylococcus epidermidis as gram-negative and gram-positive surrogates, respectively, we...