Giant bacteria trade antibiotics for resistance as lifestyles shift

Giant sulfur-oxidizing bacteria, among the largest and most visually striking prokaryotes known, appear to reorganize their accessory genomes according to how they live, according to a new genomic survey published in Environmental Microbiome. The study compared free-living chemolithoautotrophs with host-associated symbiotic relatives and found a striking trade-off: lineages living inside hosts carried far more antimicrobial resistance genes but had lost much of their capacity to biosynthesize secondary metabolites.

The analysis covered 82 genome assemblies representing eight taxa. These lineages independently evolved gigantism and contrasting lifestyles, offering a natural comparative framework for asking how lifestyle shapes the accessory genome — the portion of the genome beyond core housekeeping and chemolithoautotrophy functions, which had remained poorly characterized in these bacteria.

The researcher screened the assemblies with a battery of computational tools. Putative antimicrobial resistance genes were identified using DeepARG and ABRicate; biosynthetic gene clusters were detected with antiSMASH; defense systems with DefenseFinder and CRISPRCas++; and plasmids and prophages with geNomad, PHASTEST, VirSorter2 and PhaMer, followed by quality filtering with CheckV. Phage protein co-evolution was assessed with HyPhy, including the GARD and BGM methods. Lifestyle-associated differences were tested statistically with negative-binomial models that used genome size as an offset, an important control in organisms whose genomes span enormous size ranges.

After curation, the survey retained 214 high-confidence putative antimicrobial resistance genes and 350 biosynthetic gene clusters. Symbiotic lineages were strongly enriched in resistance genes, with an incidence rate ratio of 4.60, but depleted in total biosynthetic gene cluster density, with a ratio of 0.55. That depletion was driven by the loss of several major cluster classes: nonribosomal peptide synthetases, terpene clusters, polyketide synthases and arylpolyene clusters. Enrichment of RiPP clusters — ribosomally synthesized and post-translationally modified peptides — partially offset the loss.

Defense systems, the genetic arsenals bacteria use against phages and other invaders, showed a different pattern. Their distribution was heterogeneous across the sampled taxa, and genus-level differences largely disappeared once genome size was taken into account, suggesting that much of the apparent variation in defense content scales with genome size rather than lifestyle.

The spatial relationship between defense genes and biosynthetic gene clusters also drew attention. Defense open reading frames were not enriched inside biosynthetic cluster cores, but they were modestly over-represented within a 50 to 100 kilobase neighborhood around those clusters, hinting at a looser genomic association rather than tight functional embedding.

Mobile genetic elements proved elusive. The survey recovered ten plasmids and eleven curated prophage-like sequences, and most of these showed limited similarity to entries in public databases. That scarcity of matches indicates that the mobile gene pool of giant sulfur bacteria remains poorly represented in current reference collections, a gap that complicates efforts to interpret horizontal gene transfer in these lineages.

Co-evolutionary signals within phage proteins were uneven as well. The evidence for co-evolution was stronger in structural phage proteins than in lytic and tail-associated proteins, suggesting that different functional modules of phages experience different evolutionary pressures during their interaction with these unusual hosts.

Taken together, the findings indicate that giant sulfur bacteria reallocate accessory genomic investment between biosynthetic capacity and antimicrobial resistance depending on lifestyle: free-living chemolithoautotrophs maintain a richer secondary-metabolite repertoire, while their symbiotic, fermentative relatives lean instead on resistance determinants. The study is a genomic survey of a limited set of assemblies, and the resistance genes are putative calls from computational tools rather than experimentally verified functions. Even so, the work sketches a coherent picture of how gigantism, symbiosis and genome architecture intersect in some of the largest bacteria on Earth, and it underscores how much of their accessory biology still awaits discovery in public sequence databases.

Subject of Research: Accessory genome evolution, antimicrobial resistance genes and mobile elements in giant sulfur-oxidizing bacteria with free-living and symbiotic lifestyles

Article Title: Accessory genome evolution in giant bacteria: antimicrobial resistance, secondary metabolism, and phage–host coevolution in free-living and symbiotic lineages

Article References: Rahimian, M. (2026). Accessory genome evolution in giant bacteria: antimicrobial resistance, secondary metabolism, and phage–host coevolution in free-living and symbiotic lineages. Environmental Microbiome. https://doi.org/10.1186/s40793-026-00981-w

Image Credits: AI Generated

DOI: 10.1186/s40793-026-00981-w

Keywords: giant bacteria, Beggiatoaceae, Thiomargarita, Epulopiscium, antimicrobial resistance genes, biosynthetic gene clusters, prophages, plasmids, symbiosis, genomics, defense systems, phage coevolution