Genesis of antibiotic resistance LVII: Antibiotic resistance gene repertoire (ARGR) Roulette (Padmavyūha or Chakravyūha Model) Impugn CRISPR‐Cas‐9 conferred antibiotic sensitivity
Authors: Villarreal Diego , De Los Santos Ludwig , Escalante Jesus , Trevino Roland , Fuentes Liliana , Balino Armando , Kannan Subburaj 
Published: April 2020

A hypothetical scheme is presented to delineate the plausible cause for the slump of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) ‐ Cas9: “CRISPR‐associated protein 9”) labyrinthine gene editing of ARGR would gleam a catastrophic augmentation leading to an evolution of virulent bacterial pathogen(s) dithering sensitivity to antibiotics, impairing the effective treatment of antibiotic resistance bacterial pathogens induced sepsis, exacerbating disseminated intravascular coagulation (DIC) unto antibiotic resistance pandemic (ARP). Given the fact that AR is developmental malady enthralling intensive critical care inclusive of fluid resuscitation in a clinical emergency (patient cohort of sepsis treated with EGDT trial NCT01663701 resulting in‐hospital mortality.) A comparative model as intricate as CRISPR‐Cas‐9, while as sacrosanct as Chakravyūha: Chakra (spinning wheel), a strategy: (“vyuh”), with the lotus flowerets (Padmavyuh) made of seven circular paths characteristic of constant movement to that of a spiral down pattern of clustered regularly interspaced paths to the center core with strongest forces to mount resistance compare to that of the first layer with entrance ( Exhibit B1:
https://www.youtube.com/watch?v=oy3Qzt74V6Q; Exhibit B2:
https://youtu.be/hHc705uTOWc) was analyzed to derive an imperative of gene editing and its amelioration of antibiotic resistance. As suggested by the presenters, the formulation to break Chakravyūha is to increase the deployment of force in the following format per each path: force deployment per path would be 1/7 = 0.142857 where the denominator = total paths; whereas numerator is the specific number of path in the Chakravyūha. Therefore for path one force required to break and/or to overcome the resistance is = 1/7 = 0.142857142857; for path two = 0.142857 × 2 = 0.28571142857; for path three 0.142857 × 3= 0.428571142857; for path four 0.142857 × 4= 0.57142857142857; for path five = 0.142857 × 5 = 0.7142857142857; for path 0.142857 × 6 = 0.857142857142857; for path seven = 0.142857 × 7 = 0.857142857142857; and path seven @ core = 0.142857 × 7 = 0.999999142857 considered rounding off to 1. The unique six digits, 142857 is repeated among all paths similar to the basis of gene editing compare the Exhibit A: time 0.55 – 3.50 min; to that of the Exhibit B1: time:6.11 – 7.25 min & 2: Exhibit B2 time 5.51 – 7.25 for mitigating the AR by targeting and editing of antibiotic resistance genes (ARG) in ARGR would lead an increased inactivation of preexisting ARG conferring sensitivity to antibiotics benefiting the antibiotic therapy but not clinically evolving AR which is predominantly regulated by infection specific antibiotic regimen of a patient’s life span tacit of multifactorial inclusive of exposure to multitude AR bacteria (ARB) at different stages of life span, and patient specific clinical history. Treatment options where in which inherent off target errors of gene editing by CRISPR‐Cas9’s and inability to match the rate of commission versus correction [to that of errors in breaking of Chakravyūha ] of ARG unique to sepsis.

Support or Funding Information

Supported by PD funds by SWTJC to Subburaj Kannan