Colistin, also called polymyxin E, occupies a special and precarious position in modern medicine. It is a cationic polypeptide that attacks the outer membrane of Gram-negative bacteria, and after decades of limited use because of kidney toxicity, it was reintroduced in recent years as a final defense against multidrug-resistant infections. With few new antibiotics in the development pipeline, clinicians increasingly depend on colistin when carbapenem-resistant pathogens strike hospital patients. The emergence of bacteria that resist this drug is therefore not a routine scientific concern but a genuine emergency in global public health, and the new study demonstrates that the ocean may be serving as an unexpected reservoir and highway for the genes responsible.

The mechanics of colistin resistance matter for understanding why the new results are so significant. Resistance can arise in two ways. Intrinsic resistance develops through chromosomal mutations that alter lipid A, the lipopolysaccharide component of the bacterial outer membrane that colistin targets, reducing the drug’s ability to bind. Acquired resistance, by contrast, depends on the horizontal transfer of mcr genes, usually carried on plasmids, which are mobile DNA elements that can shuttle between bacterial cells. Since the discovery of the mcr-1 gene in Escherichia coli plasmids a decade ago, researchers have identified ten mcr variants, from mcr-1 through mcr-10, and watched them disperse across continents, animal populations, and clinical settings. What remained poorly understood was how extensively these genes had colonized marine ecosystems.

To answer that question, the Brazilian team designed a natural experiment spanning roughly 330 kilometers of the Rio de Janeiro coastline plus the Fernando de Noronha Archipelago, a volcanic island group about 360 kilometers offshore in the Western Atlantic. Their sampling sites deliberately covered a gradient of human influence. At one extreme sat Bom Jesus Cove in Guanabara Bay, a tropical urban estuary receiving raw sewage, oils, and industrial contaminants from Rio de Janeiro city. At the other extreme lay the submarine caves of Fernando de Noronha, protected within a national marine park and accessible only by SCUBA diving. Between those poles, the researchers sampled the Cagarras Archipelago, a no-take marine protected area unfortunately positioned near the Ipanema submarine sewage outfall; the biodiverse waters of Arraial do Cabo, including the Gruta Azul submarine cave; and Ilha Grande Bay, one of the world’s largest tropical bays, which faces growing pressure from coastal settlements and maritime traffic.

The laboratory work was methodical and technically demanding. From 1,550 total bacterial isolates, the team focused on 308 Gram-negative bacilli identified as potential hosts of acquired colistin resistance determinants. Bacteria were cultured on Luria Bertani and MacConkey agar from water samples, washed and swabbed from pieces of floating plastic, and extracted from sponge tissue through serial dilution across four growth media. Identification proceeded by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry on a Bruker Microflex LT platform, and DNA was extracted using a thermal lysis protocol with Chelex 100 resin. Polymerase chain reaction screening then probed each strain for eight mcr variants, and any positive strains were tested further for beta-lactamase genes, quinolone resistance genes, aminoglycoside resistance genes, sulfonamide resistance genes, and class 1, 2, and 3 integron-integrase genes.

The results were striking in both breadth and detail. Of the 308 potential host strains, 101 carried at least one mcr variant, generating 128 total gene occurrences. Water samples contributed 59.4 percent of the positive strains, plastic litter 35.6 percent, and marine sponges 5.0 percent. The mcr-9 variant dominated with 33 occurrences, followed by mcr-3 with 23, mcr-2 with 18, and mcr-1 with 17. That mcr-9 topped the list is noteworthy because global metagenomic surveys have often ranked mcr-1 as the most dispersed variant. The mcr-9 gene is known to circulate on IncHI2 plasmids that interconnect human, animal, and environmental isolates, suggesting an efficient dissemination network that the ocean may now be extending.

The bacterial hosts carrying these genes were equally concerning. Among ten identified genera, Enterobacter, Acinetobacter, Vibrio, and Klebsiella predominated. Enterobacter species alone accounted for 31 strains and harbored the greatest mcr diversity, with every variant except mcr-5 and mcr-7 detected in the genus. More alarming still, mcr-positive Enterobacter was not confined to polluted Bom Jesus Cove but turned up in marine sponges and cave waters in Fernando de Noronha, an area with restricted human access. One Enterobacter hormaechei strain, isolated from a sponge in Sapata Cave, simultaneously carried mcr-2, mcr-9, and the sulfonamide resistance gene sul1. Four strains carried three mcr variants at once, including Klebsiella pneumoniae isolates from pristine sponges and from floating plastic, and an Enterobacter cloacae from Noronha water. Both K. pneumoniae and E. cloacae belong to the notorious ESKAPE group of pathogens, and their carriage of multiple resistance genes in aquatic matrices highlights the risk of waterborne transmission to humans.

The co-occurrence of resistance genes painted an even darker picture. Nearly half of the mcr-positive strains, 46.5 percent, also carried other antimicrobial resistance genes or integron-integrases, with sulfonamide resistance genes, particularly sul1, the most frequent companions, followed by the beta-lactamase genes blaTEM and blaSHV. In Bom Jesus Cove, the team detected the carbapenemase gene blaKPC alongside mcr-3 in Enterobacter bugandensis and Raoultella ornithinolytica strains, a combination that effectively eliminates two of the last therapeutic options for infections caused by these organisms. Integron-integrases, genetic platforms that capture and shuffle gene cassettes, co-occurred with mcr exclusively in the polluted cove, suggesting bacterial adaptation to intense anthropogenic selective pressure. Because changes in membrane permeability in mcr-positive bacteria can reduce sensitivity to multiple drugs, these combinations can compound into true multidrug resistance, complicating treatment of hospital-associated infections.

The gradient of pollution left a measurable fingerprint on the data. In Bom Jesus Cove, 27 of 104 water-isolated strains tested positive for mcr, and 36 of 82 strains from floating plastic litter carried the genes, a prevalence of roughly 44 percent that represents the highest in the study. The finding positions plastic debris as both a reservoir and a vector for antimicrobial resistance, offering microbes a stable, drifting substrate on which biofilms can form, exchange genes, and travel with currents. At the Cagarras Archipelago, 40 percent of water-isolated strains were positive despite formal protection, a legacy of the nearby sewage outfall. Arraial do Cabo showed 36.5 percent prevalence among water isolates and Ilha Grande Bay 36.3 percent. In Fernando de Noronha, prevalence dropped to about 5 percent of candidate host strains, with two of 17 water isolates and five of 15 sponge isolates positive, proving that resistance persists even where human pressure is minimal.

What emerges from the study is a warning that antimicrobial surveillance cannot remain confined to clinics and farms. Marine sponges, submarine caves, and drifting plastic are now documented hotspots of colistin resistance, and the genes involved sit on mobile elements capable of jumping into human pathogens. The Brazilian coastline, with its juxtaposition of dense urban pollution and remote protected archipelagos, offered an ideal natural laboratory, but the pattern it revealed is almost certainly global. The researchers argue for integrated monitoring programs that treat the ocean as a critical node in the antimicrobial resistance network, alongside conservation strategies that reduce sewage discharge and plastic pollution. As colistin remains a last resort for patients out of options, every mcr gene circulating in seawater, attached to plastic, or sheltering inside a sponge represents a card stacked against future medicine, and the ocean, it turns out, is dealing them freely.

Subject of Research: Distribution of mobile colistin resistance (mcr) genes in bacteria from Brazilian marine environments

Article Title: Widespread occurrence of mobile colistin resistance genes in Brazilian marine environments

Article References: Brunelli, R. C., de Jesus Carvalho Baptista, T. V., de Oliveira Nithack Marques, M., da Silva Oliveira Alves, G., Abdon, B. B., Mello, M. P., Paranhos, R., Gallo, M. N., Vinzon, S. B., Lage, A., Sandes, J., Muricy, G., Klautau, M., Lopes, M. V., Dias, G. R., Canellas, A. L. B., & Laport, M. S. (2025). Widespread occurrence of mobile colistin resistance genes in Brazilian marine environments. Ocean Microbiology, 1(1), Article 3. https://doi.org/10.1186/s44375-025-00003-z

Image Credits: AI Generated

DOI: 10.1186/s44375-025-00003-z

Keywords: antimicrobial resistance, colistin, mcr genes, marine microbiology, plastic pollution, Guanabara Bay, Fernando de Noronha, Enterobacter, Klebsiella pneumoniae, integrons, marine sponges, One Health

The scale of the analysis is itself remarkable. Drawing on publications indexed in PubMed, Embase, and Web of Science, and following the PRISMA reporting guidelines, the research team—which included investigators from Shahid Beheshti University of Medical Sciences, Tehran University of Medical Sciences, Alborz University of Medical Sciences, and collaborating institutions in Iran—extracted resistance data from clinical isolates worldwide. Of the 245 included studies, 106 focused on K. pneumoniae, 89 on P. aeruginosa, 42 on E. coli, and 8 on S. maltophilia. Pooled prevalence estimates with 95 percent confidence intervals were calculated using random-effects meta-analysis in Stata version 18, with subgroup analyses stratified by continent, publication year, and the laboratory method used to detect resistance. That methodological detail matters: colistin susceptibility testing is notoriously unreliable with automated systems, and the gold-standard broth microdilution method is not always used, a source of heterogeneity the authors explicitly accounted for.

The headline numbers tell a story of divergent fortunes across species. The pooled global prevalence of colistin resistance stood at 5.9 percent for P. aeruginosa and 4.0 percent for E. coli—troubling, but still comparatively contained. K. pneumoniae, however, showed a pooled resistance rate of 20.6 percent, meaning that in the hospital wards captured by these studies, roughly one in five clinical isolates of this notoriously drug-resistant pathogen no longer responded to the antibiotic of last resort. Most alarming of all was S. maltophilia, an opportunistic pathogen that disproportionately infects immunocompromised and critically ill patients, where pooled resistance reached 38.5 percent. Because colistin is among the few options available for some S. maltophilia infections, a resistance rate approaching four in ten isolates represents a genuinely precarious therapeutic situation.

Geography sharpened the picture considerably. At the country level, higher prevalence estimates for P. aeruginosa were observed in Canada, India, and Spain; for K. pneumoniae in Brazil and Greece; and for E. coli in China and Turkey. For S. maltophilia, elevated rates were reported in countries where data exist but remain sparse, including Colombia, Thailand, and Hungary. This patchiness is a finding in its own right. The authors highlight the scarcity of data from Oceania in particular, along with the limited number of studies from several countries, as critical gaps in global surveillance. Resistance does not respect borders, and the regions where no one is measuring may be precisely where the problem is spreading unobserved.

Beneath the prevalence statistics lies a second layer of the analysis: the molecular identity of the resistant strains. Using multilocus sequence typing and, in a subset of studies, whole-genome sequencing, the review identified dominant clonal lineages driving colistin resistance. In P. aeruginosa, sequence type ST235 dominated overwhelmingly, accounting for 58.0 percent of typed resistant isolates—a clone with an international reputation for virulence and multidrug resistance. In K. pneumoniae, ST101 was the most frequently identified lineage at 29.0 percent, a sequence type long associated with carbapenem-resistant hospital outbreaks. In E. coli, two lineages shared the spotlight, with ST131 and ST69 each representing 10.6 percent of typed isolates. ST131 in particular is among the most successful extraintestinal pathogenic E. coli clones ever documented, and its presence among colistin-resistant isolates underscores how resistance genes can piggyback on globally disseminated successful strains.

The genetics of resistance itself emerged as perhaps the most consequential finding. Colistin kills bacteria by binding to lipopolysaccharide, the negatively charged lipid anchor of the outer membrane of Gram-negative bacteria. Resistance typically arises when bacteria chemically modify that target—adding phosphoethanolamine or other moieties that reduce colistin binding. Since the discovery in 2015 that this modification can be encoded by plasmid-borne mcr genes, the specter of horizontally transferable colistin resistance has haunted antimicrobial resistance research: unlike chromosomal mutations, plasmid-mediated resistance can jump between species and strains with alarming efficiency. The meta-analysis found that the mcr-1 variant—the first and still most widespread plasmid-mediated colistin resistance gene—was overwhelmingly dominant. It accounted for 100 percent of resistant P. aeruginosa isolates in which mcr variants were reported, 97.8 percent of resistant E. coli isolates, and 57.4 percent of resistant K. pneumoniae isolates. Notably, no mcr variants were reported in S. maltophilia, whose resistance presumably rests on other mechanisms, including intrinsic and adaptive modifications of its lipopolysaccharide or related membrane structures.

The predominance of mcr-1 across three of the four species carries a double warning. First, it suggests that the plasmid-mediated resistance machinery that first emerged in livestock and food animals has fully entrenched itself in human clinical populations worldwide. Second, because mcr-1 typically co-occurs on plasmids carrying other resistance determinants—carbapenemases, extended-spectrum beta-lactamases—its continued dominance implies that colistin resistance is not traveling alone but as part of packages of pan-drug resistance. The scenario that infectious disease specialists have long feared, in which a plasmid carrying both a carbapenemase gene and an mcr gene arrives in a single successful K. pneumoniae clone, is not hypothetical; the high resistance rates in K. pneumoniae documented in this analysis suggest it is already unfolding in substantial pockets of the world.

The detection methods underlying these estimates also reveal a structural weakness in the field. Across the included studies, colistin susceptibility was assessed by broth microdilution—the reference method recommended by clinical standards bodies—by epsilometer gradient tests, and by a range of disk diffusion and automated systems, the latter of which are known to produce discordant results for polymyxins. The subgroup analyses by detection method, alongside stratification by continent and publication year, exposed meaningful heterogeneity in the pooled estimates, a reminder that part of the global variation in reported resistance reflects not just true biological differences but differences in how laboratories measure the phenomenon. Minimum inhibitory concentration testing, MALDI-TOF-based identification of isolates, pulsed-field gel electrophoresis, and whole-genome sequencing were variably deployed across the evidence base, with higher-resolution methods concentrated in wealthier countries—a further source of surveillance bias.

What emerges from the synthesis is a call to action that the authors frame in explicitly global terms. Colistin resistance, they conclude, remains a significant and expanding threat among major Gram-negative pathogens worldwide, with substantial geographical variation in resistance prevalence, sequence type distribution, and mcr gene profiles. The high resistance rates observed in certain regions, they argue, emphasize the urgent need for coordinated international surveillance, antimicrobial stewardship programs, and targeted infection control strategies to limit the dissemination of colistin-resistant strains. In practical terms, that means standardized polymyxin susceptibility testing in all clinical laboratories, aggressive screening and containment of high-risk clones such as ST235 P. aeruginosa and ST101 K. pneumoniae, and rational restriction of colistin use in both human medicine and agriculture, where the drug’s continued use in animal feed remains a plausible reservoir for mcr-1.

For clinicians, the message is sobering but not fatalistic. A global resistance rate of 4 to 6 percent in E. coli and P. aeruginosa still leaves colistin useful in most infections caused by those organisms, provided susceptibility is confirmed by reliable testing. But the 20.6 percent rate in K. pneumoniae and the 38.5 percent rate in S. maltophilia transform treatment decisions in settings where those pathogens dominate—intensive care units, neonatal units, and wards housing ventilator-associated pneumonia, contexts the review’s underlying studies frequently describe. Empirical use of colistin without susceptibility confirmation is increasingly a gamble in high-prevalence regions. And because the review’s evidence base draws on studies published through 2025, the picture it paints is a floor, not a ceiling; the trajectory of resistance documented in year-stratified analyses points upward for at least some organism-region combinations.

The study also carries a quieter methodological legacy. By systematically cataloguing sequence types and mcr variants across a quarter-century of literature and four bacterial species simultaneously, it provides a baseline against which future surveillance can be measured—a common reference frame for a problem that has too often been studied in fragments. As the authors and the broader antimicrobial resistance community emphasize, the antibiotics pipeline remains thin, and for some MDR Gram-negative infections there is nothing behind colistin at all. Protecting the last line of defense, this analysis makes clear, is no longer an abstract aspiration but an epidemiologically urgent, geographically mapped, and molecularly characterized imperative.