Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bacteria is a major global health concern due to high antimicrobial resistance (nearly all antibiotics) and high mortality rates as high as 30–60%. Klebsiella pneumoniae causes both community- and hospital-acquired infections, including pneumonia, sepsis, and urinary tract infections, and is responsible for ~10% of nosocomial infections. Moreover, the “hyper-virulent” strains and community-acquired pyogenic liver abscess (PLA) caused by K. pneumoniae have been reported worldwide, more prevalent in Asia in the last two decades. Serotypes K1 and K2 have been identified as major virulence factors in K. pneumoniae liver abscess and are more prevalent strains, accounting for 70% of all isolates. Although K1 and K2 capsular types are more prevalent strains associated with invasive infections, no vaccine against K. pneumoniae is available.
Motivation:
As the pipeline of a new class of antibiotics is draining out, vaccine strategies against resistant bacteria have become an effective alternative approach. A bioconjugate vaccine comprising K1-/K2 CPS conjugated to endotoxin A (EPA), which provided protection from extremely lethal hypervirulent isolates, represents the first case. Hence, a semisynthetic approach towards the development of K2 CPS would be an attractive approach to tackle the AMR issue of K. pneumoniae. There are no prior synthetic studies reported for this molecule.