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population was low. Another independent study revealed the presence of tetracycline
in the late Roman period skeletons of Egypt (Armelagos 1969, Cook et al. 1989).
These observations underline the fact that ancient civilizations used materials containing tetracycline as part of their diet.
Alexander Fleming’s serendipitous-yet-miraculous discovery of Penicillin in
1928 revolutionized the method of treatment. Although molds were used to combat
infectious diseases by different civilizations during ancient times, Fleming’s persistent pursuance on the topic and the purification methods perfected by Howard
Florey and Ernst Chain led to mass production and clinical use of Penicillin (Chain
et al. 1940). This molecule was rightly nicknamed as “wonder drug” following its
ability to cure deadly diseases such as syphilis, gangrene, and tuberculosis. Much
before the discovery of Penicillin and its first clinical use in 1940s, the foundation
stone for “antibacterial chemotherapy” had already been laid by Paul Ehrlich. In
1909 he discovered Salvarsan, a synthetically derived compound which was used to
treat syphilis (Ehrlich and Hata 1910). This event is remembered not only for the
discovery of an antimicrobial compound but also for the introduction of a systematic screening procedure for drug discovery, that resulted in the identification of
thousands of drugs and their subsequent clinical use. Following Ehrlich’s methodology, Gerhard Domagk tested Prontosil, a sulfa drug synthesized by Josef Klarer and
Fritz Mietzsch, in 1935 and found that it is effective against many important bacterial infections in mice (Chain et al. 1940). The discovery of Penicillin, Salvarsan,
and Prontosil inspired the scientific community, which resulted in the discovery of
many antimicrobials and clinical use of some of them.
13.3 Need of Novel Sources
As man was broadening his arsenal with more and more antimicrobial agents and
inching toward victory over pathogens by complete eradication of infectious diseases, the microbes were in preparation of a silent revolt – antimicrobial resistance.
WHO defines antimicrobial resistance as the “resistance of a microorganism to an
antimicrobial drug that was originally effective for treatment of infections caused
by it.” Various reasons are attributed to microbial drug resistance that include
selective pressure, mutation, horizontal gene transfer (HGT), etc. Due to the development of resistance of pathogens to various drugs, the treatment regimen was
redefined to include more than one drug in order to kill those pathogens which
could be resistant to one (or more) of the drugs in the cocktail. The sigh of relief
did not last longer as microbes decided to win the race against man by developing
worse strategies of drug resistance of various degrees. Emergence of multidrugresistant (MDR) pathogens such as Mycobacterium tuberculosis, Campylobacter
jejuni, Clostridium difficile, Escherichia coli, Haemophilus influenzae, Klebsiella
pneumoniae, Pseudomonas aeruginosa, Salmonella spp., Serratia spp.,
Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, etc. collapsed
treatment plans (Davies and Davies 2010), and extremely drug resistant (XDR) and
totally drug resistant (TDR) strains of M. tuberculosis made treatments practically
13 Novel Sources of Antimicrobials
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