Elimination of intracellular microbes using drug combination therapy and unveiling survival mechanism of host cells upon microbial invasion

Abstract

Intracellular microbes are actively present in various tumor types in low biomass and play a major role in metastasis. Eliminating intracellular microbes on a cellular level with precision remains a challenge. To address this issue, we designed a screening pipeline to characterize intracellular microbes and their interaction with host cells. We used host and microbial in vitro lab-based constant and reproducible model, host as (mammalian cancer HeLa), and microbial strain as (Escherichia coli 25922). To study the pharmacological impact on intracellular bacterial load, we used antibiotics (ampicillin, roxithromycin, and ciprofloxacin) and chemotherapy drugs (doxorubicin and cisplatin) as external stimuli for both host and microbes. We found that increasing pharmacological stress does not increase microbial load inside the host cells. Eliminations of intracellular bacteria was done by using permutation orthogonal arrays (POA), whereby we acquired optimal drug combination in particular sequence of drugs, which reduced 90%–95% of the intracellular microbial load. Proteomic analysis revealed that upon invasion of Escherichia coli 25922, HeLa cells enriched ATP production pathways to activate intermediate filaments, which should be investigated closely via in vivo models.