Sensor histidine kinases kdpD and aauS regulate biofilm and virulence in Pseudomonas aeruginosa PA14.

Pseudomonas aeruginosa is a multidrug-resistant opportunistic human pathogen that utilizes two-component systems (TCSs) to sense pathophysiological signals and coordinate virulence. P. aeruginosa contains 64 sensor histidine kinases (HKs) and 72 response regulators (RRs) that play important roles in metabolism, bacterial physiology, and virulence. However, the role of some TCSs in virulence remains uncharacterized. In this study, we evaluated the virulence potential of some uncharacterized sensor HK and RR knockouts in P. aeruginosa using a Galleria mellonella infection model. Furthermore, we demonstrated that KdpD and AauS HKs regulate virulence by affecting P. aeruginosa biofilm formation and motility. Both ΔkdpD and ΔaauS showed reduced biofilm and motility which were confirmed by restored phenotypes upon complementation. Moreover, ΔkdpD and ΔaauS exhibited increased survival of HeLa cells and G. mellonella during in vivo infection. Altered expression of the transcriptional regulators anR and lasR, along with the virulence genes lasA, pelA, cupA, pqsA, pqsB, pqsC, and pqsD in the mutant strains elucidated the mechanism by which ΔkdpD and ΔaauS affect virulence. These findings confirm that kdpD and aauS play important roles in P. aeruginosa pathogenesis by regulating biofilm formation and motility.

Roles of Two-Component Systems in Pseudomonas aeruginosa Virulence.

Pseudomonas aeruginosa is an opportunistic pathogen that synthesizes and secretes a wide range of virulence factors. P. aeruginosa poses a potential threat to human health worldwide due to its omnipresent nature, robust host accumulation, high virulence, and significant resistance to multiple antibiotics. The pathogenicity of P. aeruginosa, which is associated with acute and chronic infections, is linked with multiple virulence factors and associated secretion systems, such as the ability to form and utilize a biofilm, pili, flagella, alginate, pyocyanin, proteases, and toxins. Two-component systems (TCSs) of P. aeruginosa perform an essential role in controlling virulence factors in response to internal and external stimuli. Therefore, understanding the mechanism of TCSs to perceive and respond to signals from the environment and control the production of virulence factors during infection is essential to understanding the diseases caused by P. aeruginosa infection and further develop new antibiotics to treat this pathogen. This review discusses the important virulence factors of P. aeruginosa and the understanding of their regulation through TCSs by focusing on biofilm, motility, pyocyanin, and cytotoxins.

Implants For Extracapsular Neck Of Femur Fracture Dynamic Hip Screw Versus Intramedullary Nailing.

Neck of femur fractures are the most prevalent type of injury in elderly trauma patients. Both intra and extra capsular type of fractures are equally distributed in the given population. Traditionally, Extra capsular fractures are fixed with Dynamic Hip screw or Intra medullary nailing based on the type of fracture. NICE (National Institute of Clinical Excellence) recommends fixing 31-A1 and 31-A2 fractures with DHS (Dynamic Hip Screw) whereas AO recommends fixing 31-A1 with DHS and 31-A2.1 subtype with DHS and 31-A2.2 and 31-A2.3with IMN (Intra medullary nail). In regional trauma centre 178 patients, 125 females and 53 males with extra capsular neck of femur fractures fixed were selected in a retrospective study. The data was spanning over a period of 1 year. Fractures were classified as per AO classification by two registrars. The implant selection was analysed in terms of the short term out come to find out the cost effectiveness of one over the other. The quality of reduction was assessed as per standard criteria and consideration of lateral femoral wall thickness was taken into account to assess the stability of fracture. The study found more risk of peri prosthetic fractures associated with Intra medullary nailing as compared to Dynamic Hip screw and more risk of Varus collapse was found to be associated with DHS as compared to IM Nail. Moreover, despite of Nail being costly as compared to DHS, the study did not reveal its superiority in terms of inpatient hospital stay. In appropriately selected patient DHS provides results in terms of hospital stay, revision rate and wound complications comparable to IM Nail in the short term justifying its use in the above-mentioned fracture patterns as per the standard National Institute of clinical Excellence guidelines.