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Editorial
. 2024 Mar;14(3):e1600.
doi: 10.1002/ctm2.1600.

Using permeation guidelines to design new antibiotics-A PASsagE into Pseudomonas aeruginosa

Brett N Cain  1 , Paul J Hergenrother  1
Affiliations
Editorial

Using permeation guidelines to design new antibiotics-A PASsagE into Pseudomonas aeruginosa

Brett N Cain et al. Clin Transl Med. 2024 Mar.
No abstract available

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Figures

FIGURE 1
FIGURE 1
Differences in outer membrane physiology and permeation guidelines for gram‐negative bacteria Escherichia coli and Pseudomonas aeruginosa, with eNTRy‐rule compliant compounds able to enter E. coli through porins, and PASsagE (Pseudomonas aeruginosa Self‐promoted Entry)‐compliant compounds entering via the self‐promoted uptake pathway. Source: Parameters taken from Richter et al. and Geddes et al. .
FIGURE 2
FIGURE 2
(A) A retrospective consideration of the conversion of tetracycline to tigecycline, a version more active against wild‐type Pseudomonas aeruginosa. Notably, these two compounds have similar target engagement as judged by nearly identical minimum inhibitory concentration (MIC) values against an efflux‐deficient strain of P. aeruginosa PAO1 (0.25 µg/mL and 0.125 µg/mL respectively); accumulation values are in units of nmol/1012 CFUs. The green box represents the PASsagE‐compliant region. (B) The value of certain nitrogenous functional groups in enhancing physiochemical parameters important for P. aeruginosa uptake. Values calculated using cyclohexane with the represented functional groups appended, using molecular operating environment (MOE) after assessing the compounds protonation state at physiological pH. HBD, hydrogen bond donor.
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