Susceptibility to Urinary Tract Infection: Benefits and Hazards of the Antibacterial Host Response

Abstract

A paradigm shift is needed to improve and personalize the diagnosis of infectious disease and to select appropriate therapies. For many years, only the most severe and complicated bacterial infections received more detailed diagnostic and therapeutic attention as the efficiency of antibiotic therapy has guaranteed efficient treatment of patients suffering from the most common infections. Indeed, treatability almost became a rationale not to analyze bacterial and host parameters in these larger patient groups. Due to the rapid spread of antibiotic resistance, common infections like respiratory tractor urinary-tract infections (UTIs) now pose new and significant therapeutic challenges. It is fortunate and timely that infectious disease research can offer such a wealth of new molecular information that is ready to use for the identification of susceptible patients and design of new suitable therapies. Paradoxically, the threat of antibiotic resistance may become a window of opportunity, by encouraging the implementation of new diagnostic and therapeutic approaches. The frequency of antibiotic resistance is rising rapidly in uropathogenic organisms and the molecular and genetic understanding of UTI susceptibility is quite advanced. More bold translation of the new molecular diagnostic and therapeutic tools would not just be possible but of great potential benefit in this patient group. This chapter reviews the molecular basis for susceptibility to UTI, including recent advances in genetics, and discusses the consequences for diagnosis and therapy. By dissecting the increasingly well-defined molecular interactions between bacteria and host and the molecular features of excessive bacterial virulence or host-response malfunction, it is becoming possible to isolate the defensive from the damaging aspects of the host response. Distinguishing "good" from "bad" inflammation has been a long-term quest of biomedical science and in UTI, patients need the "good" aspects of the inflammatory response to resist infection while avoiding the "bad" aspects, causing chronicity and tissue damage.

Bacterial infections and patterns of antibiotic use in patients with COVID‐19

“…Studies have shown that susceptibility to such infections can be an indicator of defective innate mucosal immune system with resultant failure to distinguish and mount a response to commensal pathogens. 32 Another possible explanation is the high prevalence of diabetes mellitus in our study, which make the studied population susceptible to UTI. 33 Mortality was observed in 50% of our COVID-19 patients with concomitant bacterial infection (OR, 5.838; P < .0001).…”

Bacterial coinfections in COVID: Prevalence, antibiotic sensitivity patterns and clinical outcomes from a tertiary institute of Northern India

“…[ 18 ] The increase in the mortality rates may also be attributed to the older population involved with bacterial coinfections along with the presence of other comorbidities. [ 30 ] The older population has a weakened immune system due to immunosenescence, and hence, succumb to the infections more easily than the younger ones. These people, therefore, more likely, require interventions in the form of intubation, mechanical ventilation, and the use of vasopressive drugs to improve the outcome and increase their life expectancy.…”

NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression

“…Further investigation of the impact of DMF and NRF2 activation on long-term bacterial persistence in bladder and bladder immune response is also needed. Our work underscores the importance of NRF2 activation for driving UPEC exocytosis via RAB27B and balancing ''good'' and ''bad'' inflammatory responses to combat invasive pathogens without excessive tissue damage (Ambite et al, 2016a(Ambite et al, , 2016b.…”