Biology subjects

Dobihal, G. S.

Publications and source records attributed to Dobihal, G. S..

3 recordsLinked to original sources

bioRxiv2025

A novel post-translational modification of fimbriae drives pathogenicity in Klebsiella pneumoniae

Multi-drug resistant Gram-negative bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKp), are a public health emergency. The predominant CRKp sequence type worldwide is ST258. However, the factors underlying ST258s epidemic success are not well defined. The understudied two-component system CrrAB is a genomic feature of ST258 and has been hypothesized to contribute to its global dominance. Despite this, the molecular details underpinning CrrABs contribution to ST258 pathogenicity are not well understood. We used RNA-sequencing to identify the regulon of CrrA and found that CrrAB induces the expression of a novel gene, encoding Crr-regulated fimbriae modifying protein (CfmP). CfmP post-translationally modifies fimbriae to significantly increase host cell adhesion and high bacterial loads within the host, consequently increasing ST258 virulence. CrrAB also drives high antibiotic resistance in CRKp. Thus, our data places CrrAB at the intersection of virulence and antibiotic resistance supporting its function as an important regulatory system driving the pathogenicity of ST258.

microbiology↗

bioRxiv2022

WhyD tailors surface polymers to prevent bacteriolysis and direct cell elongation in Streptococcus pneumoniae

Penicillin and related antibiotics disrupt cell wall synthesis in bacteria and induce lysis by misactivating cell wall hydrolases called autolysins. Despite the clinical importance of this phenomenon, little is known about the factors that control autolysins and how penicillins subvert this regulation to kill cells. In the pathogen Streptococcus pneumoniae (Sp), LytA is the major autolysin responsible for penicillin-induced bacteriolysis. We recently discovered that penicillin treatment of Sp causes a dramatic shift in surface polymer biogenesis in which cell wall-anchored teichoic acids (WTAs) increase in abundance at the expense of lipid-linked lipoteichoic acids. Because LytA binds to these polymers, this change recruits the enzyme to its substrate where it cleaves the cell wall and elicits lysis. In this report, we identify WhyD (SPD_0880) as a new factor that controls the level of WTAs in Sp cells to prevent LytA misactivation and lysis. We show that WhyD is a WTA hydrolase that restricts the WTA content of the wall to areas adjacent to active PG synthesis. Our results support a model in which the WTA tailoring activity of WhyD directs PG remodeling activity required for proper cell elongation in addition to preventing autolysis by LytA.

microbiology↗

bioRxiv2017

Genome-wide phenotypic analysis of growth, cell morphogenesis and cellcycle events in Escherichia coli.

Cell size, cell growth and the cell cycle are necessarily intertwined to achieve robust bacterial replication. Yet, a comprehensive and integrated view of these fundamental processes is lacking. Here, we describe an image-based quantitative screen of the single-gene knockout collection of Escherichia coli, and identify many new genes involved in cell morphogenesis, population growth, nucleoid (bulk chromosome) dynamics and cell division. Functional analyses, together with high-dimensional classification, unveil new associations of morphological and cell cycle phenotypes with specific functions and pathways. Additionally, correlation analysis across ~4,000 genetic perturbations shows that growth rate is surprisingly not predictive of cell size. Growth rate was also uncorrelated with the relative timings of nucleoid separation and cell constriction. Rather, our analysis identifies scaling relationships between cell size and nucleoid size and between nucleoid size and the relative timings of nucleoid separation and cell division. These connections suggest that the nucleoid links cell morphogenesis to the cell cycle.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC=\"FIGDIR/small/101832_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@63d469org.highwire.dtl.DTLVardef@e7117org.highwire.dtl.DTLVardef@22a436org.highwire.dtl.DTLVardef@4b0167_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗