Biology subjects

Nizam, S.

Publications and source records attributed to Nizam, S..

3 recordsLinked to original sources

bioRxiv2025

Long-term control of Salmonella after transient T3SS-2 inhibition

Anti-virulence approaches are promising alternatives for traditional antibiotics to control bacterial infections. Several inhibitors show impressive activities in animal infection models, but the relative contribution of specific virulence inhibition vs off-target effects on both the bacteria and host remain unclear. Here, we developed Salmonella with switchable virulence by putting the type 3 secretion system-2 (T3SS-2) which is essential for systemic virulence, under the control of doxycycline. In infected mice given low-dose doxycycline in drinking water, the strain showed normal fitness and virulence. Doxycycline withdrawal shut down T3SS-2, arrested Salmonella replication and resolved disease symptoms. After ten days of T3SS-2 inhibition, reintroducing doxycycline restored replication, but bacterial loads remained stable, indicating strengthened host immunity. These effects were comparable to treatment with fluoroquinolone antibiotics, a highly effective therapy for human systemic salmonellosis. Thus, selective T3SS-2 inhibition may offer a suitable alternative for controlling invasive Salmonella infections.

microbiology↗

bioRxiv2020

Super LeArner Prediction of NAb Panels (SLAPNAP): A Containerized Tool for Predicting Combination Monoclonal Broadly Neutralizing Antibody Sensitivity

SummarySingle broadly neutralizing antibody (bnAb) regimens are currently being evaluated in randomized trials for prevention efficacy against HIV-1 infection. Subsequent trials will evaluate combination bnAb regimens (e.g., cocktails, multi-specific antibodies), which demonstrate higher potency and breadth in vitro compared to single bnAbs. Given the large number of potential regimens in the research pipeline, methods for down-selecting these regimens into efficacy trials are of great interest. To aid the down-selection process, we developed Super LeArner Prediction of NAb Panels (SLAPNAP), a software tool for training and evaluating machine learning models that predict in vitro neutralization resistance of HIV Envelope pseudoviruses to a given single or combination bnAb regimen, based on Envelope amino acid sequence features. SLAPNAP also provides measures of variable importance of sequence features. These results can rank bnAb regimens by their potential prevention efficacy and aid assessments of how prevention efficacy depends on sequence features. Availability and ImplementationSLAPNAP is a freely available docker image that can be downloaded from DockerHub (https://hub.docker.com/r/slapnap/slapnap). Source code and documentation are available at GitHub (respectively, https://github.com/benkeser/slapnap and https://benkeser.github.io/slapnap/). ContactDavid Benkeser, benkeser@emory.edu

bioinformatics↗

bioRxiv2018

The fungal root endophyte Serendipita indica modifies extracellular nucleotides to subvert plant immunity

One sentence abstractImmune modulation by metabolites in plant fungus interaction\n\nAbstractExtracellular adenosine 5'-triphosphate (eATP) is an essential signaling molecule that mediates different cellular processes through its interaction with membrane-associated receptor proteins in animals and plants. eATP regulates plant growth, development and responses to biotic and abiotic stresses. Its accumulation in the apoplast induces ROS production and cytoplasmic calcium increase mediating a defense response to invading microbes. We demonstrate that perception of eATP is important in plant-fungus interaction and that during colonization by the beneficial root endophyte Serendipita indica accumulation of eATP in the apoplast occurs at early symbiotic stages. We show by liquid chromatography-tandem mass spectrometry, cytological and functional analysis that S. indica subvert eATP host response by secreting SiE5NT, an enzymatically active ecto-5'nucleotidase capable of hydrolyzing eATP to adenosine. A. thaliana lines producing extracellular SiE5NT are signi?cantly better colonized and have reduced eATP levels and defense signaling, indicating that SiE5NT functions as a compatibility factor. Our data show that extracellular bioactive nucleotides play an important role in fungus-root interactions and that fungi can modify plant derived metabolites in the apoplast to modulate host immunity.

plant biology↗