Biology subjects

Haldar, A.

Publications and source records attributed to Haldar, A..

5 recordsLinked to original sources

bioRxiv2026

Pantoea agglomerans T6SS effectors reside in hotspots with combinatorial offensive and defensive arsenals

Gram-negative bacteria deploy type VI secretion systems (T6SSs) to mediate interbacterial competition. Although numerous T6SS effectors have been identified, their pan-genomic repertoires and evolutionary dynamics remain poorly understood. Here, we combine proteomics and comparative genomics to map the T6SS effector landscape across Pantoea agglomerans, a diverse species that includes pathogenic and beneficial strains. We uncover an extensive pan-genomic arsenal in which most effectors are encoded outside the main T6SS gene cluster, within highly dynamic hotspots distributed across the chromosome and megaplasmids. Analysis of these hotspots reveals multilayered, combinatorial arrangements of shuffled genetic cargo. Remarkably, these loci act as versatile "genomic armories" that co-localize offensive antibacterial weapons with protective anti-phage defense systems. By investigating uncharacterized genes within these variable regions, we discovered and validated a novel T6SS effector and a previously unknown anti-phage defense system, named Juno. Collectively, our findings demonstrate that bacterial warfare arsenals are highly modular and reside in dynamic genomic hubs that alternate or combine interbacterial aggression with viral defense. This evolutionary association reveals a functional blurring between offensive and defensive strategies within the bacterial accessory genome. Our findings further highlight orphan effector-associated variable regions as promising leads in the search for unrecognized bacterial conflict and defense systems.

microbiology↗

bioRxiv2026

Transition Metal-Weak Organic Acid Synergy Enables Rapid Bactericidal and sporicidal Activity

The global rise in antibiotic-resistant bacteria underscores the urgent need for alternative antimicrobial strategies capable of limiting bacterial growth and viability. We previously demonstrated that weak organic acids and transition metals combine synergistically to strongly inhibit bacterial growth. Here, we extend these findings to determine whether this interaction results only in bacteriostatic suppression or can induce irreversible killing. Using standardized quantitative assays, selected acid-metal combinations achieved rapid bactericidal activity, producing >5-log reductions in Gram-negative and Gram-positive bacterial load after brief exposure at concentrations substantially lower than those required for many conventional disinfectants. This activity extended beyond vegetative cells. Bacillus cereus spores, used as a surrogate for spores of Bacillus anthracis, exhibited significant loss of viability under defined conditions. Given the environmental persistence of anthrax spores and their relevance in biological threat scenarios, these findings have implications not only for antimicrobial resistance mitigation but also for biodefense and environmental decontamination. Sporicidal efficacy was exposure dependent, with prolonged contact enabling effective killing at reduced concentrations. Together, these results establish acid-metal systems as scalable antimicrobial agents with bactericidal and sporicidal activity relevant to public health and global security. Importance statementAntibiotic resistance and the persistence of bacterial spores demand new antimicrobial strategies that are both effective and practical. This study shows that combining weak organic acids with transition metals transforms two modest antimicrobial agents into a powerful broad-spectrum killing system. These synergistic formulations rapidly eradicate Gram-negative and Gram-positive bacteria, achieving bactericidal activity at concentrations substantially lower than those used in many conventional disinfectants. Importantly, their activity extends to bacterial spores, among the most resilient biological structures known and a major challenge in environmental decontamination and biodefense. Using Bacillus cereus as a surrogate for Bacillus anthracis, we demonstrate dramatic sporicidal activity, reducing spore viability by up to six orders of magnitude. By coupling strong efficacy with a simple, scalable, and potentially environmentally compatible formulation, this work establishes transition metal-organic acid combinations as a promising new platform for infection control, environmental decontamination, and biodefense preparedness.

microbiology↗

bioRxiv2025

Phage-encoded homing endonucleases attenuate bacterial immunity

The arms race between bacteria and bacteriophages (phages) gave rise to multiple layers of antagonistic mechanisms, many of which remain unexplored. Here, we investigated the anti-phage defense system GAPS4 and showed that it is a non-selective DNase triggered by sensing DNA breaks. We further demonstrated that this activation mechanism renders GAPS4 a double-edged sword, sensitizing bacteria to various forms of antibacterial antagonism. Using comparative genomics, we found that phage-encoded homing endonucleases, long considered selfish mobile genetic elements, enhance phage fitness by attenuating GAPS4-mediated immunity. Our findings shed light on the evolutionary advantage provided by these ubiquitous mobile elements to their host phages, and on the intricate evolutionary cross-talk between bacteria and their predators.

microbiology↗

bioRxiv2023

Differential expansion and retention patterns of LRR-RLK genes across plant evolution

To maximize overall fitness, plants must accurately respond to a host of growth, developmental, and environmental signals throughout their life. Many of these internal and external signals are perceived by the leucine-rich repeat receptor-like kinases, which play roles in regulating growth, development, and immunity. This largest family of receptor kinases in plants can be divided into subfamilies based on conservation of the kinase domain, which demonstrates that shared evolutionary history often indicates shared molecular function. Here we investigate the evolutionary history of this family across the evolution of 112 plant species. We identify lineage-specific expansions of the malectin-domain containing subfamily LRR subfamily I primarily in the Brassicales and bryophytes. Most other plant lineages instead show a large expansion in LRR subfamily XII, which in Arabidopsis is known to contain key receptors in pathogen perception. This striking asymmetric expansion may reveal a dichotomy in the evolutionary history and adaptation strategies employed by plants. A greater understanding of the evolutionary pressures and adaptation strategies acting on members of this receptor family offers a way to improve functional predictions for orphan receptors and simplify identification of novel stress related receptors.

genomics↗

bioRxiv2020

Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock

Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two distinct LPS receptors TLR4 and caspase-4. Whereas the regulation of TLR4 activation by extracellular and phago-endosomal LPS has been studied in great detail, auxiliary host factors that specifically modulate recognition of cytosolic LPS by caspase-4 are largely unknown. This study identifies dynamin-related membrane remodeling proteins belonging to the family of Immunity related GTPases M clade (IRGM) as negative regulators of caspase-4 activation in macrophages. Phagocytes lacking expression of mouse isoform Irgm2 aberrantly activate caspase-4-dependent inflammatory responses when exposed to extracellular LPS, bacterial outer membrane vesicles or gram-negative bacteria. Consequently, Irgm2-deficient mice display increased susceptibility to caspase-4-mediated septic shock in vivo. This Irgm2 phenotype is partly reversed by the simultaneous genetic deletion of the two additional Irgm paralogs Irgm1 and Irgm3, indicating that dysregulated Irgm isoform expression disrupts intracellular LPS processing pathways that limit LPS availability for caspase-4 activation.

immunology↗