Genesis of Antibiotic (Ab) Resistance (AR) XXXVI: “Hormesis Activate resident AR Genes (ARG) to Functional Antibiotic Resistance Genes (FARG) in Yanomami Amerindians (YA) During Swarming”.

YA are mountain people who were first contacted in the mid‐1960s, and who continue to live seminomadic hunter‐gatherer lifestyles in the Amazon jungle of Venezuela. YA harbor bacteria that carry FARG, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements (verbatim) (Sci Adv. 2015 Apr 3; 1(3)). An effort has been made to provide the rationale for the presence of FRAG in YA genome even in the absence of exposure to commercial antibiotics. I. Acquiring the ARG from the soil commensal bacteria and activated upon exposure to Ab became FRAG, II. Having a diverse group of resident bacterial colonies with ARG upon exposure to Ab, the bacteria became adapted to form FRAG, III. Induction of ARG to FRAG by active metabolic compounds acquired from herbal remedies to the active form, IV. Horizontal Gene transfer mediated acquirement of ARG or FRAG from the gold miners referred as “Garimpeiros” through microevolution, V. Exposure/Inhalation of Particulate Matter (PM) (EHP. 2015 Apr;123(4):337–43.) induced “Cline” (cline is a steady change in certain characteristics present by members of the same population of the same species). During a cline, a species deals with mutations and variation, to be better adapted to the new environment, but their bacteria is also dealing with mutations and variations which will make it resistant to most forces. Yanomami's never actually knew they were having contact or taking antibiotics because they took them unknowingly. This could have also happened because the bacteria could have had silent antibiotics in them. So when the Yanomami's where exposed to bacteria, they were also being exposed to antibiotics, IV. Through “Persistence, V. Through intrinsic resistance is when the bacteria have the ability to protect it from the attacks of the antibiotics (Nature. 2016; 533:212–6. Hormesis ‐ Int J Mol Sci. 2017 Jan 15; 18(1). In essence, due to the fact that YA is nomadic (Hunter‐Gatherer) mode of life moving from one location to other location in the deep forest in groups are constantly exposed to low dose of the PM in the air. At the initial stage there may have been causality (Altruistic Death) conferring survival advantage to YA transforming a sensitive state to more tolerant to PM, through “Hormesis” enabling the inactive ARG to adapt and form FRAG by a process known as Collective Antibiotic Resistance (CAT) (Nat Chem Biol. 2015 Mar; 11:182–188). It is speculated that the resident bacteria in the gastrointestinal tract (GI) of YA may have evolved “swarming” state (surface growth) while initiating “quorum sensing (QS), forming a biofilm on the skin surface as well as GI. Swarming phenotype of bacteria has been shown to confer survival advantage via the altruistic death of initial population directly exposed to antibiotic and subsequent increase in the density of Ab tolerant and/or resistant pathogenic bacteria (J.Bac. 2003; 185:3111; PNAS. 2010; 107:3776). It is also a strong possibility that as inhabitants of the “Amazon River” basin, could have acquired water‐borne bacterial pathogen with FRAG in the form of consumption, irrigation and sewage disposal. Taken together, YA does not have to be consuming antibiotics or infected by AR pathogens to become resistant and engender FRAG. As per our hypothetical scheme, all of the above mechanisms could be contributing to the intrinsic AR. The degree of FARG in the genome of YA and resident commensal microbiome of YA directly proportional to extent of the exposure and tolerance to PM. Support or Funding Information Supported by Professional Development funds to Subburaj Kannan This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .