PubMed · 16697754
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Meta J Kuehn. 2006. Genetically engineered probiotic competition.. https://doi.org/10.1053/j.gastro.2006.03.031
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OBJECTIVES: Multidrug-resistant (MDR) Campylobacter infections are an increasing clinical concern, as rising fluoroquinolone (FQ) resistance leaves macrolides as the primary treatment option. We investigated multidrug resistance in clinical Campylobacter samples from Germany. METHODS: We analyzed 6980 clinical isolates (2010-2022), performing phenotypic susceptibility testing and sequencing on 2912 genomes. Cultures showing multidrug resistance were studied using scanning electron microscopy (SEM). RESULTS: We found that 453 (6%) Campylobacter samples were resistant to both FQ and macrolides. Two of the C. jejuni samples were resistant to antibiotics from ten different classes. Genome analysis revealed that these samples, despite being derived from single colonies, contained >10% Enterococcus DNA reads. SEM confirmed the presence of coccoid bacteria interspersed with spiral-shaped Campylobacter. Additional culture-based purification resulted in pure C. jejuni isolates that retained FQR but lost macrolide resistance. The presence of MDR Enterococcus spp. in the mixed samples protected C. jejuni from above-MIC (minimum inhibitory concentration) concentrations of several ribosome-targeting antimicrobials whereas pure Campylobacter were susceptible. CONCLUSIONS: The impact of microbial interactions on resistance phenotypes is poorly understood. We show that close interactions with highly resistant intestinal bacteria can induce multidrug resistance phenotypes in Campylobacter. These findings highlight that microbial context shapes antibiotic resistance and may influence treatment outcomes.
It is generally believed that molecular mimicry between bacterial lipooligosaccharide (LOS) and nerve glycolipids may play an important pathogenic role in immune-mediated peripheral neuropathy. One of the putative infectious agents is Campylobacter jejuni (C. jejuni). To elucidate the structural basis for the molecular mimicry, we investigated the structure of the lipooligosaccharide (LOS) fraction of C. jejuni, strain HS19, and found that it includes at least two components, characterized as fast-and slow-moving bands (LF and LS) by thin-layer chromatography as revealed by cholera toxin B subunit (Ctxb) overlay. Structural analysis of the oligosaccharide portion of LS established that it had the following structure: Gal-GalNAc-(NeuAc)Gal-Hep-(Glc;PO(3)H)Hep-Kdo. The GM1-like epitope was validated by a terminal tetrasaccharide unit within this structure. On the other hand, analysis of LF revealed an entirely different structure: 1, 4'-bisphosphoryl glucosamine disaccharide N, N'-acylated by 3-(2-hydroxytetracosanoyloxy)octadecanoic acid at 2- and 2'-positions, which is consistent with that of lipid A. No GM1-like epitope was observed in LF. Both LS and LF interacted with Ctxb as demonstrated by TLC-overlay and sucrose density gradient centrifugation. Surprisingly, LF does not have the basic GM1 structure for interacting with Ctxb. Instead, the affinity of LF to Ctxb required that one or both of the phosphate groups be present in the glucosamine disaccharide residue because after alkaline phosphatase treatment the dephosphorylated LF was unable to bind to Ctxb. We conclude that LS is likely the component contributing to GM1-mimicry in autoimmune peripheral neuropathy and that the role of LF is not clear but may be associated with the initial activation of autoreactive T cells.
In Campylobacter jejuni, a gram-negative bacterial pathogen causing gastroenteritis in humans, the CmeR regulatory protein controls transcription of the multidrug transporter gene operon cmeABC. CmeR belongs to the TetR family of transcriptional regulators. The 210-residue CmeR consists of two functional motifs: an N-terminal DNA-binding domain and a C-terminal ligand-binding domain. It is predicted that the DNA-binding domain interacts directly with target promoters, while the C-terminal motif interacts with inducing ligands (such as bile salts). As an initial step towards confirming this structural model, recombinant CmeR protein containing a 6 x His tag at the N-terminus was crystallized. Crystals of ligand-free CmeR belonged to space group P2(1)2(1)2, with unit-cell parameters a = 37.4, b = 57.6, c = 93.3 A. Diffraction was observed to at least 2.2 A at 100 K. Analysis of the detailed CmeR structure is currently in progress.