Proteus mirabilis isolates have been intensively researched for their capacity to cause urinary tract infections (UTIs) and their swarming motility, although little is known about this phenomenon. Probiotic Lactobacillus species, which are beneficial bacteria, are being studied worldwide as therapeutic and preventative agents against bacterial infections. This study investigated Lactobacillus supernatants as a potential new treatment against Proteus mirabilis. In addition to testing their antimicrobial and anti-swarming activities, the research also aimed to understand the genetic mechanisms behind the observed phenotypic changes. Methods. A total of 150 urine specimens were collected from UTI patients at various hospitals in Baghdad. Direct culture was performed by streaking the specimens on differential media. RNA was extracted and purified from the bacterial isolates, and then reverse transcription and quantitative PCR were used to evaluate swarming-related gene expression. Gene expression was assessed relative to a reference gene to reveal how probiotics regulate swarming behavior at the genetic level. Gene expression patterns varied, indicating complex genomic responses to Lactobacillus exposure. Results. UTIs affected 50 males (33.33%) and 100 females (66.66%) of various ages. Proteus mirabilis was identified in 30 (20%) of the 150 samples. Resistance was observed in 25 (83.33%) isolates for azithromycin and amoxicillin/clavulanic acid, and in 22 (73.33%) isolates for meropenem. Real-time PCR showed significant alterations in the expression of four swarming-related genes (rsbA, umoD, ZapA, and FliL). The rsbA gene showed a notable increase in expression, while another sample displayed a decrease. The umoD gene exhibited the largest change, with expression doubling in some cases. ZapA showed the greatest increase, nearly tripling in expression in one sample. FliL expression also rose in multiple isolates. Swarming activity was positively correlated with gene expression levels for rsbA (r = 0.8, p = 0.009), umoD (r = 0.635, p = 0.045), ZapA (r = 0.942, p = 0.001), and FliL (r = 0.894, p = 0.001). Conclusions. The study reveals a complex gene network regulating the swarming motility of Proteus mirabilis. It suggests that Lactobacillus acidophilus supernatants can modify gene expression and bacterial motility, potentially aiding in the treatment of UTIs.
