Medical needs

ESKAPE pathogens

Gram-negative & Gram-positive bacteria

Bacteria are a type of unicellular, prokaryotic organisms that inhabit almost every environment on earth, including the skin and gut of animals and humans (typically good bacteria). Bacteria are categorized into two types, Gram-positive (G+) and Gram-negative (G-), based on the structure of their cell walls and how they show-up in a Gram stain (mycobacterium tuberculosis (TB) is a special case – structurally G+ but sometimes staining like G- due to presence of mycolic acid in the cell wall). The cell walls of G+ bacteria are made up of a thick, layer of peptidoglycan, whereas G- bacteria have only a thin layer in their cell wall, however, they also have an outer membrane. This outer membrane is not present in G+ bacteria.

The greater understanding of microbes and the role of hygiene in medicine increased human life expectancy in the late 1800, which was then improved dramatically ever since penicillin was discovered by Sir Alexander Fleming and mass produced for WWII in the 1940s. However, Fleming himself already warned of resistance in an interview soon after winning the Nobel Prize in 1945 for discovering penicillin:

"The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism."

Flemming was of course talking about antimicrobial resistance (AMR) arising through natural selection pressure of antibiotics, and AMR has been accelerated by the extensive use and overuse of antimicrobials in humans, animals and with antibiotics having entered into the environment since their widespread introduction.

The use and misuse of antibiotics has led to an increase in resistant pathogenic bacteria such as the ESKAPE (Enterococcus faecium (G+), Staphylococcus aureus (G+), Klebsiella pneumoniae (G-), Acinetobacter baumannii (G-), Pseudomonas aeruginosa (G-), and Enterobacter species (G-); also including E. Coli (G-)) pathogens, which are a leading cause of nosocomial infections in healthcare setting. ESKAPE are a major source of concern as these bacteria have and continue to acquire resistance to antibiotics through spontaneous resistance development, and in some cases through the transmission of resistance genes between one another.

One of the world’s most dangerous ESKAPE bacteria and on the WHO’s and CDC number 1 priority list of pathogens, is Acinetobacter baumannii. Acinetobacter was often referred to as Iraqibacter, since it first plagued wounded soldiers who served in the Iraq war in the early 2000s, with resistant strains rapidly spreading through military facilities and then subsequently into US civilian hospitals. Now, highly resistant forms of A. baumannii are found across the globe due to greater global travel. The standard of care antibiotic used to treat A. baumannii infections is a Carbapenem, however Carbapenem resistant A. baumannii (CRAB) is now widespread with rates in the USA at >60%, in southern Europe typically 65-95% and in China >70%, leading to mortality rates from hospital acquired infections of ≥50%.