Neisseria gonorrhoeae *Ketol-Acid Reductoisomerase Is a Potential Therapeutic Target DOI: http://dx.doi.org/10.5772/intechopen.107993*

microbes will be indiscriminately killed or inhibited. Notably, different antibiotics or their combinations have different antimicrobial spectra and will result in different damages to the microbiome. The disruption of gut microbiota contributes to numerous diseases, including diabetes, obesity, autism, and superinfection in critically ill patients.

Under normal physiological conditions, the microbiota maintains a homeostatic state. It also plays a crucial role in many aspects of physiological processes, including maintaining the integrity of the gut mucosal barrier, promoting the development of the immune system, and protecting against enteric pathogens. Inappropriate antibiotics impact host immunity by altering the bacterial metabolites and the signals transmitted from gut microbiota to the host (intestinal epithelial cells and intestinal immune cells).

Because antibiotic administration elicits many side effects, restriction of the overuse of antibiotics is imperative. However, it is unrealistic to completely abandon antibiotics in clinical practice, especially for patients with severe infections. Therefore, safe strategies should be proposed to attenuate and/or avoid antibioticinduced microbial dysbiosis and gut microbiome disruption. Firstly, intravenous administration of KARI's inhibitors drugs (or adjuvant) may avoid the gut flora alteration. The adjuvant administration can be followed by the administration of PRRs agonist, or probiotics. Indeed, the probiotic intervention is able to reduce the antibiotic-associated diarrhea [27]. A recent study suggested that co-administration of probiotics and antibiotics prevents *C. difficile* infection in patients receiving antibiotics [28]. On the other hand, gut microbiota transplantation is a new strategy able to control intestinal inflammation and restore the intestinal homeostasis.

KARI's inhibitors remain a good alternative for external treatment for dermatological infections like staphylococcal skin infections in deep wounds. The external application or the intravenous administration of the drug will avoid the alteration of gut flora. Even with need for an oral administration of these drugs, the disorder of gut flora will be partial, due to the high population density of a healthy microbiome, compared to pathogens. Therefore, probiotics can help to maintain the gut flora in sufficient density to maintain the gut mucosal barrier.

Moreover, KARI is an attractive target for the development of new biocides. Some tested KARI's inhibitors inhibit the enzyme in the nanomolar range [29]. Furthermore, the study of KARI-expression during bacterial host-infection may confer new insight on the importance of these targets in the pathogen metabolism and growth. The investigation of the effect of potent KARI's inhibitors on pathogen growth in the presence or not of appropriate antibiotic allow further progress toward the understanding of the inhibitor's effect on pathogen and hosthomeostasis, and the development of new inhibitors that specifically target KARIs in pathogenic processes.
