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Transfer RNAs (tRNAs) and their modifications are central to bacterial translation and physiology, yet their roles in stress adaptation remain underexplored. While extensively studied in eukaryotes, and linked to diseases, bacterial tRNA modifications are only recently gaining attention. This review highlights emerging insights into how tRNA modifications and associated enzymes contribute to bacterial survival under oxidative and antibiotic stresses, both disrupting proteostasis. We examine the environmental and physiological stresses bacteria encounter, focussing on reactive oxygen species and sub-lethal antibiotic exposure. These stresses challenge proteome integrity and trigger adaptive responses involving key stress regulators. We explore the expanding field of bacterial epitranscriptomics, detailing the diversity, dynamics and structural impact of tRNA modifications, and how they influence selective translation. Central to this is the concept of modification tunable transcripts, linking specific codon usage patterns to stress-responsive translation reprogramming. Beyond their catalytic roles, tRNA-modifying enzymes also have additional functions. We discuss this dual functionality and its broader implications for bacterial adaptability. By integrating recent technological advances and conceptual models, this review underscores the potential of targeting tRNA modifications as a novel strategy to combat bacterial pathogenicity and antibiotic resistance. With many aspects still unresolved, the study of bacterial tRNA modifications promises rich opportunities for discovery and therapeutic innovation.

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load. Acute viral infection results in ACE2 downregulation. This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function. The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.

Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts. A bacterial family of cGAS/DncV-like nucleotidyltransferases synthesizes a diverse range of cyclic dinucleotide and trinucleotide compounds that are likely to modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.

In the era of increasing bacterial antibiotic resistance, finding new ways of combating pathogens is especially important. An attractive possibility is targeting bacterial survival strategies that microorganisms employ either to evade the host immune-responses or to adapt to the hostile environment encountered once inside the host. An example of the latter is the stringent response, mediated by guanosine penta- and tetra-phosphate, collectively referred to as (p)ppGpp. These molecules (alarmones) are responsible for switching bacterial gene expression and metabolism to allow survival under various stresses, such as nutritional deprivation and oxidative stress. (p)ppGpp turnover is mediated by various enzymes belonging to the RSH (RelA-SpoT homolog) family, some of which are capable of both, (p)ppGpp synthesis and hydrolysis, while others can perform only one of these functions. In this minireview, we discuss strategies that aim to disrupt or modulate the stringent response either by inhibiting these enzymes or on the contrary – enhancing their activities, as that goal can be achieved by several ways, i.e. blocking (p)ppGpp synthesis, inducing its synthesis or blocking its hydrolysis.

Bacteria must coordinate their growth rate, shape, and division to survive and flourish, yet how these cellular properties are maintained in the face of environmental stresses is poorly understood. Working with Escherichia coli , we show that activating the Rcs phosphorelay, an envelope stress-signaling system, in the absence of external stresses slows growth, shortens cells, and increases the concentration of the key division protein FtsZ, leading to more closely spaced division sites. Depleting the levels of IgaA, a regulator of the Rcs pathway, yielded similar phenotypes. However, activating Rcs via drug-induced cell-wall disruption did not affect growth rate, indicating that the physiological impact of this pathway depends on the context of activation. Our findings reveal links among cell growth, shape homeostasis, and cell envelope stress. Understanding this coupling further will provide new avenues to predict and modulate bacterial growth and physiology during stress.

The wide abuse of antibiotics has accelerated bacterial multiresistance, which means there is a need to develop tools for rapid detection and characterization of bacterial response to antibiotics in the management of infections. In the study, an electrochemical biosensor based on nanoporous alumina membrane and graphene quantum dots (GQDs) was developed for bacterial response to antibiotics detection. Anti-Salmonella antibody was conjugated with amino-modified GQDs by glutaraldehyde and immobilized on silanized nanoporous alumina membranes for Salmonella bacteria capture. The impedance signals across nanoporous membranes could monitor the capture of bacteria on nanoporous membranes as well as bacterial response to antibiotics. This nanoporous membrane and GQD-based electrochemical biosensor achieved rapid detection of bacterial response to antibiotics within 30 min, and the detection limit could reach the pM level. It was capable of investigating the response of bacteria exposed to antibiotics much more rapidly and conveniently than traditional tools. The capability of studying the dynamic effects of antibiotics on bacteria has potential applications in the field of monitoring disease therapy, detecting comprehensive food safety hazards and even life in hostile environment.

Despite the plant health-promoting effects of plant microbiota, these assemblages also comprise potentially detrimental microbes. How plant immunity controls its microbiota to promote plant health under these conditions remains largely unknown. We find that commensal bacteria isolated from healthy Arabidopsis plants trigger diverse patterns of reactive oxygen species (ROS) production dependent on the immune receptors and completely on the NADPH oxidase RBOHD that selectively inhibited specific commensals, notably Xanthomonas L148. Through random mutagenesis, we find that L148 gspE , encoding a type II secretion system (T2SS) component, is required for the damaging effects of Xanthomonas L148 on rbohD mutant plants. In planta bacterial transcriptomics reveals that RBOHD suppresses most T2SS gene expression including gspE . L148 colonization protected plants against a bacterial pathogen, when gspE was inhibited by ROS or mutation. Thus, a negative feedback loop between Arabidopsis ROS and the bacterial T2SS tames a potentially detrimental leaf commensal and turns it into a microbe beneficial to the host. The plant immune output reactive oxygen species tames a detrimental bacterial commensal from native microbiota by suppressing a bacterial secretion system, allowing the co-existence and turning it into a beneficial bacterium to the host.

Recent therapeutic strategies to suppress restenosis after biliary stent placement are insufficient. Here, we demonstrate the usefulness of a self-expandable metal stent (SEMS), a stent mesh coated with silver nanoparticles (AgNPs), for suppression of both stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. The AgNP-coated SEMSs were prepared using a simple bio-inspired surface modification process. Then, the prepared SEMSs were successfully placed in 22 of 24 rabbits. Sludge formation in the AgNP-coated SEMS groups was significantly decreased compared to the control group on gross findings. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the AgNP-coated SEMS groups compared with the control group (p < 0.05 for all). There were no differences between the AgNP-coated SEMS groups (p > 0.05 for all). However, in the group coated with the greatest concentration of AgNPs (Group D), submucosal fibrosis was thicker than in the other AgNP-coated groups (p < 0.05 for all). The AgNP-coated metallic stent mesh significantly suppressed stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. Taken together, the AgNP coating strategy developed in this study could be widely utilized in non-vascular medical devices for anti-bacterial and anti-inflammatory responses.

Human taphonomic facilities (HTF) are outdoor spaces dedicated to research, educational and training activities related to human decomposition. Through the purging of decomposition by-products, a body within a HTF will generate a chemically and microbially disrupted zone of soil known as a Cadaver Decomposition Island (CDI). The biochemical dynamics of CDIs have been minimally investigated across contrasting seasons, thereby impeding our understanding of how cadaveric inputs are processed within temperate soils. This gap was addressed in a Canadian HTF by examining soil organic matter (SOM) chemistry and bacterial metabolic responses within the CDIs of donors bodies who were deposited under warm or cold seasonal conditions. Decomposition generated a pulse of SOM that was first rich in carbon then nitrogen. This was associated with an enrichment in δ13C and δ15N that was attributable to cadaveric tissues and enhanced mineralization. Fluorescence spectroscopy also revealed a transition in the molecular characteristics of organic matter that was indicative of a shift from recalcitrant terrestrial substances to labile microbial compounds. In addition, bacteria were observed to preferentially utilize carbohydrate substrates for energy production. These effects arose during the Active–Dry phases of decomposition, occurring between 13–139 days for warm deposited donors, but were delayed (31–364 days) and reduced in magnitude for cold donors. All changes were limited to the A-horizon and within a sampling radius of 20 cm from the body. These findings will inform temperate HTFs of their potential environmental impact and direct the development of soil-based forensic techniques. •Effect of human decomposition on soil biochemistry was spatially constrained.•Increases in soil carbon preceded nitrogen.•Bacterial processing altered soil organic matter lability.•Cadaveric inputs enhanced bacterial mineralization but supressed growth.•Cold season deposition led to delayed and reduced soil changes, even after warming.

Bacteria can be adapted to adverse and detrimental conditions that induce general and specific responses to DNA damage as well as acid, heat, cold, starvation, oxidative, envelope, and osmotic stresses. The stress-triggered regulatory systems are involved in bacterial survival processes, such as adaptation, physiological changes, virulence potential, and antibiotic resistance. Antibiotic susceptibility to several antibiotics is reduced due to the activation of stress responses in cellular physiology by the stimulation of resistance mechanisms, the promotion of a resistant lifestyle (biofilm or persistence), and/or the induction of resistance mutations. Hence, the activation of bacterial stress responses poses a serious threat to the efficacy and clinical success of antibiotic therapy. Bacterial stress responses can be potential targets for therapeutic alternatives to antibiotics. An understanding of the regulation of stress response in association with antibiotic resistance provides useful information for the discovery of novel antimicrobial adjuvants and the development of effective therapeutic strategies to control antibiotic resistance in bacteria. Therefore, this review discusses bacterial stress responses linked to antibiotic resistance in Gram-negative bacteria and also provides information on novel therapies targeting bacterial stress responses that have been identified as potential candidates for the effective control of Gram-negative antibiotic-resistant bacteria.