Medical application
In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, successfully treated ophthalmia neonatorum, a gonococcal infection in infants, with penicillin (fungal extract) on November 25, 1930.In 1940, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Chain, Edward Abraham, Arthur Duncan Gardner, Norman Heatley, Margaret Jennings, Jean Orr-Ewing and Arthur Gordon Sanders) at the Sir William Dunn School of Pathology, University of Oxford made progress in making concentrated penicillin from fungal culture broth that showed both in vitro and in vivo bactericidal action. In 1941, they treated a policeman, Albert Alexander, with a severe face infection; his condition improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully. In December 1942, survivors of the Cocoanut Grove fire in Boston were the first burn patients to be successfully treated with penicillin.The first successful use of pure penicillin was when Fleming treated Harry Lambert of fatal infection of the nervous system (streptococcal meningitis) in 1942. By that time the Oxford team could produce only a small amount. Florey willingly gave the only available sample to Fleming. Lambert showed improvement from the very next day of the treatment, and was completely cured within a week. Fleming published his clinical trial in The Lancet in 1943. Following the medical breakthrough the British War Cabinet set up the Penicillin Committee on 5 April 1943 that led to projects for mass production.
In Helicobacter cinaedi, there are multiple mutations in different genes that make PBP variants.Enzymatic destruction by β-lactamases is the most important mechanism of penicillin resistance, and is described as "the greatest threat to the usage [of penicillins]". It was the first discovered mechanism of penicillin resistance. During the experiments when purification and biological activity tests of penicillin were performed in 1940, it was found that E. coli was unsusceptible. The reason was discovered as production of an enzyme penicillinase (hence, the first β-lactamase known) in E. coli that easily degraded penicillin. There are over 2,000 types of β-lactamases each of which has unique amino acid sequence, and thus, enzymatic activity. All of them are able to hydrolyse β-lactam rings but their exact target sites are different. They are secreted on the bacterial surface in large quantities in Gram-positive bacteria but less so in Gram-negative species. Therefore, in a mixed bacterial infection, the Gram-positive bacteria can protect the otherwise penicillin-susceptible Gram-negative cells.There are unusual mechanisms in P. aeruginosa, in which there can be biofilm-mediated resistance and formation of multidrug-tolerant persister cells. History
Discovery
Starting in the late 19th century there had been reports of the antibacterial properties of Penicillium mould, but scientists were unable to discern what process was causing the effect. Scottish physician Alexander Fleming at St Marys Hospital in London (now part of Imperial College) was the first to show that Penicillium rubens had antibacterial properties. On 3 September 1928 he observed that fungal contamination of a bacterial culture (Staphylococcus aureus) appeared to kill the bacteria.