Biology subjects

Vellappan, S.

Publications and source records attributed to Vellappan, S..

3 recordsLinked to original sources

bioRxiv2024

Translational profiling of stress-induced small proteins uncovers an unexpected connection among distinct signaling systems

Bacterial small proteins ([≤] 50 amino acids) are an emerging class of regulators that modulate the activity of signaling networks that enable bacterial adaptation to stress. The Escherichia coli genome encodes at least 150 small proteins, most of which are functionally uncharacterized. We identified and characterized 17 small proteins induced in E. coli during magnesium (Mg2+) starvation using ribosome profiling, RNA sequencing, and transcriptional reporter assays. Several of these were transcriptionally activated by the PhoQ-PhoP two-component signaling system, which is crucial for Mg2+ homeostasis. Deletion or overexpression of some of these small proteins led to growth defects and changes in cell size under low-Mg2+ conditions, indicating physiological roles in stress adaptation. The small transmembrane protein YoaI, which was transcriptionally induced by the phosphate-responsive PhoR-PhoB signaling pathway, increased in abundance under Mg2+ limitation independently of yoaI transcription or PhoQ-PhoP signaling. YoaI activated a third signaling system, EnvZ-OmpR, which mediates responses to osmotic stress. Overall, this study establishes an initial framework for understanding how small proteins contribute to bacterial stress adaptation by facilitating cross-talk between different signaling systems. Our results suggest these proteins play broader roles in coordinating stress responses, reflecting the interconnected nature of cellular stress networks rather than strictly compartmentalized pathways responding to specific stressors.

microbiology↗

bioRxiv2024

Imaging of porphyrin-specific fluorescence in pathogenic bacteria in vitro using a wearable, hands-free system

HighlightsO_LIFluorescence imaging detects porphyrins in bacteria via natural fluorescence. C_LIO_LIA lightweight, hands-free device enables rapid, non-invasive clinical assessments. C_LIO_LIThe study tested 15 bacterial and 2 fungal strains for porphyrin-based autofluorescence. C_LIO_LI14 bacteria fluoresced on Porphyrin Test Agar, 9 on blood agar plates. C_LIO_LIThe REVEAL system aids in diagnosing infections and guiding real-time treatments. C_LI Fluorescence imaging is an effective method for detecting porphyrin production in bacteria, leveraging the natural fluorescence properties of porphyrins. Here we use a simple, lightweight, hands-free device for rapid, non-invasive assessments in clinical settings, microbial research, and diagnostic applications. Specifically in this study, we examined 15 bacterial and 2 fungal strains commonly associated with skin, oral, and/or multi-site infections at wound sites for their ability to autofluoresce based on their porphyrin production. We utilized Remel Porphyrin Test Agar and blood agar plates to monitor red fluorescence over several days of growth under aerobic or anaerobic conditions using the wearable REVEAL FC imaging system with a 405 nm violet excitation headlight paired with eyewear carrying 430 nm emission lenses. Fourteen of the fifteen bacteria produced red fluorescence when grown on Porphyrin Test Agar and nine of the fifteen bacteria also displayed red fluorescence on blood agar plates, consistent with their ability to synthesize porphyrins. Taken together, our results elucidate the sensitivity, effectiveness, and convenience of using wearable technology to detect pathogens that produce porphyrin-specific fluorescence. Consequently, the REVEAL system has immense potential to help diagnose wound infections, direct clinical procedures, and guide treatment options in real-time using fluorescence imaging all while minimizing the risk of contamination.

microbiology↗

bioRxiv2018

GrgA as a potential target of selective antichlamydials

Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particularly selective antichlamydials without adverse effects on humans and the beneficial microbiota. We previously reported that benzal-N-acylhydrazones (BAH) can inhibit chlamydiae without detectable adverse effects on host cells and beneficial lactobacilli that dominate the human vaginal microbiota among reproductive-age women. However, the antichlamydial mechanism of BAH is not known. Whereas 4 single nucleotide polymorphisms (i.e., SNP1-4) were identified in a rare Chlamydia variant with a low level of BAH resistance, termed MCR, previous studies failed to establish a causal effect of any particular SNP(s). In the present work, we performed recombination to segregate the four SNPs. Susceptibility tests indicate that the R51G GrgA allele is both necessary and sufficient for the low level of BAH resistance. Thus, the Chlamydia-specific transcription factor GrgA either is a direct target of BAH or regulates BAH susceptibility. We further confirm an extremely low rate of BAH resistance in Chlamydia. Our findings warrant exploration of GrgA as a therapeutic and prophylactic target for chlamydial infections.

microbiology↗