The K2 cps gene cluster of K. pneumoniae Chedid contains a total number of 19 open reading frames (ORFs) organized into three transcription units, orf1-2 orf3-15, and orf16-17 . In the previous studies, numerous regulatory systems were demonstrated to control the biosynthesis of CPS via regulating the cps transcriptions in K. pneumoniae, Alpelisib concentration such as the Rcs system, RmpA, RmpA2, KvhR, KvgAS, and KvhAS [17–20]. Among these, ferric uptake regulator (Fur) represses the gene expression of rcsA rmpA, and rmpA2 to decrease CPS biosynthesis [21, 22]. Therefore,
overlapping regulons governed the regulation of these assorted virulence genes in response to numerous stress conditions. Bacterial cells are constantly challenged by various environmental stresses from their natural habitats.
Similar to many gastrointestinal (GI) pathogens, K. pneumoniae faces several challenges during infection and colonisation of the human body. These include gastric acid, the immune system, and a limited supply of oxygen and nutrients [23, 24]. Among these, the concentration of iron in the environment is critical for YM155 supplier the control of cellular metabolism. Limitation of iron abolishes bacterial growth, but high intracellular concentrations of iron may damage bacteria because of the formation of undesired reactive oxygen species (ROS). Iron homeostasis maintained by the transport, storage, and metabolism of iron is tightly controlled by Fur
in many gram-negative bacteria [25–27]. To regulate gene transcription, Fur protein functions as a dimer with Fe2+ as a cofactor to bind to a 19-bp consensus sequence, called the Fur box (GATAATGATwATCATTATC; w = A or T), in the promoters of downstream genes . In several gram-negative pathogens, Fur represses the expression of genes involved in iron homeostasis and in the regulation of multiple cellular functions such as oxidative stress, energy metabolism, acid tolerance, and virulence gene production [29–32]. Janus kinase (JAK) In K. pneumoniae, Fur plays a dual role in controlling CPS biosynthesis and iron acquisition . Recently, we also found that type 3 fimbriae expression and bacterial biofilm formation were also controlled by Fur and iron availability . Therefore, the regulatory mechanism of Fur in control of multiple cellular function and virulence factors in K. pneumoniae needs to be further investigated. Although Fur typically acts as a repressor, it also functions as a check details transcriptional activator for the gene expression such as acnA fumA, and sdhCDAB (tricarboxylic acid [TCA] cycle enzymes), bfr and ftnA (iron storage), and sodB (iron superoxide dismutase [FeSOD]) [34–38]. However, positive regulation by Fur is often indirect, mediated by Fur-dependent repression of a small non-coding RNA (sRNA), RyhB .