Editorial: Host-pathogen interactions: cellular damage, death, and adaptation in microbial infections

Pathogens efficiently practice a variety of methods for their survival and to evade cellular immune mechanisms. Gram-negative bacterial pathogens such as Salmonella enterica and Vibrio parahaemolyticus specifically target mitochondria, leading to cellular stress that disrupts oxidative phosphorylation and the balance of reactive oxygen species (ROS) (1), ultimately resulting in dysfunctional mitophagy (2). This "missing link" connects acute infection to postinfectious metabolic diseases, such as insulin resistance and chronic inflammation, even after therapeutic intervention. This suboptimal immune restoration is due to unresolved cellular stress that causes long-lasting immunometabolic alteration in epithelial and adipose tissues (3). Similarly, the World Health Organization (WHO) identified Klebsiella pneumoniae as one of the top 10 serious global public health threats in the antimicrobial resistance (AMR) gram-negative category that contributes to 39% of susceptible ICU patients.Viral infections exaggerate this impediment and endorse immunometabolic alteration (4). Additionally, atmospheric particulate matter (PM) exposure, especially PM-2.5 to PM-10 particles, increases respiratory morbidity and mortality, which is directly associated with the downregulation of epithelial apoptosis and cytokines like IFN-γ (5). Even during the COVID-19 pandemic, epidemiological studies found that pre-exposure to PM may worsen SARS-CoV-2 infection aetiology and treatment outcome, although the exact cellular mechanism remains unclear (6). A few studies found PM's effects on SARC-CoV-2 infection kinetics in Calu-3 human epithelial cells when exposed to PM for 72 hr; cells were infected with the wild type Wuhan strain or the more virulent Delta strain without influencing ACE2 entry (7).Toscana virus strains shows a lot of differences. The long-lasting INMI variant stops the first IFN responses in brain organoids, which makes replication last 21 days by delaying NSs protein expression. This is different from the self-limiting SI-1812. In Drosophila models of porcine rotavirus, JAK-STAT activation elevates reactive oxygen species and antimicrobial peptides, equilibrating gut epithelial apoptosis with hyperplasia amid microbiome modifications and RNA interference evasion (8).Programmed cell death functions as a dual-edged weapon in the context of infections. Transcriptome profiling of osteomyelitis by GSVA exposes multiple programmed cell death pathways like apoptosis, autophagy, cuproptosis, and entosis, which is accompanied by immune infiltration, resulting in hub genes (SORT1, KIF1B, TMEM106B, NPC1, ATP6V0B) confirmed by qPCR for early diagnostic purposes (9). These formerly neglected non-classical deaths now highlight new treatment targets in osteomyelitis.Immune profiling improves the disclosure; leptospirosis increases CCL5, CXCL5, and CXCL9 levels, which are in line with the changes in CXCL11, CCL3, and CCL2. This makes CCL5 a diagnostic biomarker for this 15% fatal zoonosis that affects one million individuals annually (10). Nontuberculous mycobacteria (NTM), now including over 200 species, have evolved from diagnostic obscurity to prominence via molecular techniques like whole-genome sequencing, requiring customized treatment regimens post-sputum conversion (11). Polymorphisms of the vitamin D receptor (FokI and TaqI) amplify the risks of multidrug-resistant tuberculosis in highburden regions such as India, interlinking genetics, nutrition, and resistance (12).These studies focus on precision medicine. Historical insights from NTM-taxonomy challenges and cultural biases-are now integrated with line-probe assays for patient-centered care. Biomarkers from VDR mutants and chemokines allow for faster diagnosis of MDR-TB than traditional DST, which is slow and ineffective. PCD hubs, on the other hand, help separate different types of osteomyelitis. Fly intestines replicate porcine rotavirus defences, confirming Drosophila as an effective model for antiviral immunity. However, significant gaps persist, and findings from in vitro organoid models needed in vivo validation; the rise of resistance epidemics (K. pneumonia and MDR-TB) requires comprehensive solutions.This editorial highlights a biological conflict where pathogens use host machinery like mitochondrial centres, programmed cell death pathways, and mitigated cytokine and chemokine profiles lead to their supremacy. Mitochondria-focused therapies may diminish Salmonella's metabolic impact, and moderating particulate matter, especially PM10 impact, can improve post-COVID environments. Under other conditions, targeting nonstructural proteins (NSs) among neuroviruses, particularly TOSV strains, can be used for the development of vaccines by activating endogenous retinoic acid-inducible gene-I (RIG-1), and modulation in chemokine panels enhances the triage of leptospirosis.Integration of interdisciplinary essentials like genomics, transcriptomics, and various novel disease models are needed to elucidate pathogen resistance mechanisms. Policymakers should prioritise quality lifestyles, VDR screenings in endemic regions, and NTM surveillance. As zoonoses increase, such as leptospirosis and rotaviruses, these discoveries equip us to combat the perseverance of pathogens in addition to establishing robust defences based on cellular knowledge.In conclusion, research on these issues has led to a better understanding of how pathogens invade and identifying anticipatory measures that mitigate chronic consequences.