Conceptual Drug Discovery and Societal Status may not be Sufficient to Combat Multidrug-Resistant Infections

Abstract

The period between the 1940s and 1960s is commonly referred to as “the golden era of antibiotic discovery” saving million’s life and good health. However, generation and spread of multi-drug resistant bacteria are highly claiming life. MDR, XDR and PDR infections are alarming as cautioned by CDC and WHO with ten million infections worldwide. ESBL and MBL beta-lactamases (blaOXA, blaNDM1), heterogeneous acetyl/phospho/adenyl-transferases (catB3, aacC1, strA/B, aphA4, ANT) and drug efflux proteins (MFS/RND/ABC) are very much abundant in plasmids and chromosomes of most Enterobacteriaceae infections. This has happened due to three main reasons: First, mdr genes are assembled into large conjugative plasmids allowing to transfer of mdr genes into household bacteria by conjugation and secondly, drug industries are reluctant to invest in new drug discovery due to drug void following astonishingly fast mdr gene creation like blaNDM-1 and Mcr-1, inactivating carbapenems and colistin drugs that used against superbug infections; lastly, a symbiotic relation has generated signals across the bio-film for quick generation of new mdr gene against the any new oral drug consumed repeatedly. We believe abuse of multi-doses antibiotic intake without vitamins and probiotics may cause many disorders like gastrointestinal disturbances, diabetes, neurological disorders and cancer, due to death of bio-film making gut bacteria that synthesize 20 vitamins and complex bio-molecules involved in >30,000 enzymatic reactions, known as human metabolosome. Symbiotic relation is so important that 16S rRNA and 70S ribosomal proteins of bacteria are mutated as also gyrA/B and porins to withstand adverse effects of antibiotics. Many drug binding proteins have also increase the drug MIC like TetM and PenA. Due to high cost of new antibiotics, gene medicines and cancer drugs, >100,000 household are plunged into poverty line each year due to inadequate medical insurance coverage in most Asian, African and Latin American countries. As population was reached 7000 million, we need social reforms and united research agenda to lower the cost of drug. Heterogeneous phyto-antibiotics will solve the problem based on ancient Hindu and Chinese civilization but land reform is must to get enough cultivation of medicinal plants.