Fig. 6: HomI confers resistance to AH5011 hominicin.

a, b Bacterial growth curves of S. aureus strains Newman, homI expression mutant, and empty vector grown in TSB (a) or 40% v/v CM from AH5011 (b). Data represents the mean of n = 3 biological replicates and error bars show standard deviation. Statistical significance was compared to the growth of the wild-type strain Newman at 8 h using one-way ANOVA followed by Dunnett’s multiple comparison test. Exact p values from left to right are as follows: a 0.2729, 0.9983, b < 0.0001, 0.1459. c Representative images of spot-on-lawn bioactivity of AH5011 and RN4220 expressing hom BGC against lawns of S. aureus, with inhibition zone diameters represented by black dashed lines. Red dashed line indicates the limit of detection. Scale bar = 10 mm. Data represents the mean of n = 5 biological replicates, and error bars show standard deviation. Statistical significance was determined using one-way ANOVA followed by Dunnett’s multiple comparison test. Exact p values from left to right: c (diameter of AH5011 inhibition) <0.0001, 0.9743, c (diameter of AH6425 inhibition) <0.0001, 0.9921. d The HomI-hominicin complex model superimposed onto the AlphaFold model of HomI. The models are presented in a side-profile view (top) and a top-down view (bottom). Hominicin is represented in purple as sticks. HomI modeled without hominicin is represented in yellow, and HomI modeled in complex with hominicin is represented in teal. e–g The release of DiSC₃(5) from Newman wild-type (e), homI-expressing mutant (f), and empty vector (g) in the culture medium. The 8x AH5011 extract contains 32.7 µg of hominicin. Data represents the mean of n = 3 biological replicates and error bars show standard deviation. Statistical significance was compared to the untreated control group at 65 min using one-way ANOVA analysis followed by Dunnett’s multiple comparison test. Exact p values from left to right are as follows: e 0.7120, 0.0159, f (8x AH5011) 0.7705, f (8x ∆p1∆p2) 0.8201, g 0.6444, 0.0269. Source data are provided as a Source Data file.