The restriction impacts of the Type III restriction-modification system on the transmission dynamics of antimicrobial resistance genes in Campylobacter jejuni

Abstract

Introduction: The spread of antibiotic resistance genes among Campylobacter jejuni (C. jejuni) is a serious problem, and the effects of the restriction-modification (R-M) system on the transmission dynamics of these genes in C. jejuni remain poorly understood.

Materials and methods: Complete genome sequences of C. jejuni strains were extracted from the BV-BRC database until March 25, 2024. The phylogenetic and the resistance analysis were used to analyze the distribution of resistance genes in C. jejuni. The impacts of the R-M systems on the AMR genes transmission between C. jejuni strains and the possible mechanisms were explored through recombination, pangenome and mobile genetic elements analysis.

Results: C. jejuni strains carrying the Type III R-M system have a significantly lower number of antimicrobial resistance (AMR) genes compared to strains without this system (p < 0.0001), with covariance value being -0.0526. The recombination analysis also shows that the median number of the number of AMR genes in the strains not possessing the Type III R-M system increases by 19.38% compared to strains carrying that system (p < 0.0001). We also find that the horizontal gene transfer frequency might have limited relationship with the Type III R-M system in C. jejuni through pangenome and mobile genetic elements analysis.

Conclusion: Our research indicates that the Type III R-M system might restrict the transmission of AMR genes potentially by affecting recombination in C. jejuni, which provides a theoretical basis for addressing the drug resistance problem.

Keywords: Campylobacter jejuni; antibiotic resistance genes; drug resistance; restriction-modification system; transmission dynamics.

Figure 1

Heatmap of the distribution of the AMR genes in C. jejuni based on the phylogenetic tree. The rows in the heatmap represent different C. jejuni strains, and the columns represent different AMR genes. The color of the blocks represents the number of the specific AMR gene in one C. jejuni strain.

Figure 2

Differences of AMR genes in C. jejuni with or without (A) the Type I and (B) the Type III R-M system. The thicker lines in the box plot represent the median. The box plot’s upper and lower boundaries indicate the 75th (Q3) and 25th (Q1) percentiles, respectively. According to Wilcoxon-Mann–Whitney test, the number of asterisks indicates the significant differences: * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001, **** indicates p ≤ 0.0001, and ns indicates no significant difference.

Figure 3

Heatmap of the recombination in C. jejuni. The rows in the heatmap represent different C. jejuni strain genomes. The blue and red blocks represent recombination events reconstructed on the leaves and internal nodes, respectively.

Figure 4

Differences of recombination events in C. jejuni with or without the Type III R-M system. The thicker lines in the box plot represent the median. The box plot’s upper and lower boundaries indicate the 75th (Q3) and 25th (Q1) percentiles, respectively. The significance is analyzed using the Wilcoxon-Mann–Whitney test, and the number of asterisks indicates the significant differences: * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001, **** indicates p ≤ 0.0001, and ns indicates no significant difference.

Figure 5

Differences of (A) the cloud and (B) unique genes in C. jejuni with or without the Type III R-M system. The thicker lines in the box plot represent the median. The box plot’s upper and lower boundaries indicate the 75th (Q3) and 25th (Q1) percentiles, respectively. The significance is analyzed using the Wilcoxon-Mann–Whitney test, and the number of asterisks indicates the significant differences: * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001, **** indicates p ≤ 0.0001, and ns indicates no significant difference.

Figure 6

Differences of the MGE in C. jejuni with or without the Type III R-M system. The thicker lines in the box plot represent the median. The box plot’s upper and lower boundaries indicate the 75th (Q3) and 25th (Q1) percentiles, respectively. The significance is analyzed using the Wilcoxon-Mann–Whitney test, and the number of asterisks indicates the significant differences: * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001, **** indicates p ≤ 0.0001, and ns indicates no significant difference.