Host physical, chemical, and immune responses constitute well-established defences against bacterial invasion. Recent studies have highlighted the critical role of cellular mechanisms, particularly the production of reactive oxygen species (ROS) in antibacterial defence. This review focuses on ROS generation by mammalian intestinal epithelial cells (IECs) and investigates whether ROS production is host-driven to eliminate bacteria or manipulated by bacteria to suppress or exploit ROS for enhanced internalisation. We examine the activation mechanisms of the NADPH oxidase (NOX) enzyme complex and the resulting ROS production in IECs, which, unlike professional phagocytes, lack the ability to engulf bacteria. The downstream effects of NOX-mediated ROS signalling are discussed in detail. Additionally, we explore the dynamic interplay between host and pathogen, with particular attention to how bacterial infection may disrupt or hijack host NOX-mediated ROS responses. The review concludes with key experimental considerations and outlines future directions in this evolving field. Overall, we present ROS as a double-edged sword, an essential antimicrobial effector that is also susceptible to bacterial subversion, highlighting its potential as a target in novel antimicrobial strategies.

Advances in drug delivery technologies involve the extracellular vesicles as a promising bioactive drug delivery vehicle expected to improve targeted therapeutic delivery in pharmaceutical innovations. Recently, Gram‐negative bacterial extracellular vesicles (outer membrane vesicles or OMVs) have gained attention for their role in host–microbe interactions and potential in drug delivery. Bacterial extracellular vesicle (BEV) shedding is a conserved mechanism of intra‐ and interspecies communication, providing critical insights into host–microbe interactions. However, the biogenesis and compositional diversity of BEVs produced by Gram‐positive bacteria remain underexplored. Understanding the translational application potential of BEVs remains elusive due to the suboptimal isolation of BEVs and limited structural–functional characterization. A comprehensive study to develop BEVs as delivery vehicles will provide critical insights into the perspective of microbial–host interplay and illuminate the modulation of the drug delivery strategy. Here, using a food‐grade probiotic Lactococcus lacti s subsp. cremoris MG1363 (strain NZ9000), we demonstrated that perturbing peptidoglycan biosynthesis with ampicillin, which targets penicillin‐binding proteins (PBPs), significantly enhances BEV production. We further explored the interaction between BEVs and host cells through this optimized BEV biogenesis, revealing its cargo‐delivering capability. Furthermore, to understand the potential of BEVs as a multimodal drug delivery platform, we target multidrug‐resistant microbial pathogens and cancer cell proliferation with drug‐encapsulated BEVs. With a generally recognized as safe (GRAS) recognition of L. lactis, we demonstrated that drug‐loaded L. lactis BEVs can offer recognizable therapeutic effects. These findings highlight the versatile nature of L. lactis BEVs as stable, safe, natural nanocarriers capable of personalized cargo delivery with broad therapeutic applications.

Campylobacter jejuni is a leading global cause of acute foodborne gastroenteritis however, C. jejuni lacks some of the classic virulence determinants associated with other common enteric bacterial pathogens. In recent years an increasing number of C. jejuni isolates have been identified to encode Type Six Secretion System (T6SS), an apparatus utilised by Gram-negative bacteria to secrete toxic bacterial effectors into neighbouring cells. Despite the prevalence of the T6SS and previous investigations, the roles of the C. jejuni T6SS are still not well characterised especially when compared to our knowledge of other clinically relevant T6SS-positive bacterial species. Additionally, as of yet, no C. jejuni T6SS cargo effectors have been characterised. In this study, we show the C. jejuni 488 strain T6SS displays contact-dependent antagonistic behaviour towards T6SS-negative C. jejuni , Campylobacter coli , Escherichia coli and Enterococcus faecium strains suggesting the presence of the T6SS contributes to the competitive capacity of this C. jejuni T6SS-positive strain. Moreover, this antagonistic activity is linked to the functionality of CJ488_0980 and CJ488_0982, two novel putative Tox-REase-7 domain-containing effectors, which were identified through bioinformatical analysis of the C. jejuni 488 strain genome. Additionally, our investigations propose the C. jejuni 488 T6SS contributes to interaction, invasion and intracellular survival in human intestinal epithelial cells (IEC). Collectively, these initial findings are the first examples of in vitro investigation of putative cargo effectors in Campylobacter spp. and provide valuable insights into the roles of C. jejuni T6SS effectors in bacterial competition and pathogenesis. This study highlights the importance of T6SS as an emerging virulence determinant in Campylobacter spp. warranting further investigation.

Entire (fs–µs) excited state dynamics and energetics could be decoded in red-NIR emitting toxic-metal-free quantum dots (QDs), CuInS ₂ QDs.