In a finding that rewrites what scientists thought they knew about one of medicine’s most overlooked gut bacteria, researchers have completed the first large-scale genomic survey of the type VI secretion system across the genus Morganella, revealing a striking species-specific arsenal of molecular weapons. The study, published in MicrobiologyOpen, analyzed 293 clinical isolates collected between 1996 and 2023 from nine countries, and found that roughly half of all Morganella genomes harbor at least one type VI secretion system, a contractile, syringe-like nanomachine that bacteria use to fire toxic proteins into rival microbes and host cells. The results expose a deep functional divide between Morganella morganii and the recently elevated species Morganella sibonii, and suggest that these hidden weapons may shape how the bacteria compete in the gut, colonize their hosts, and even contribute to the emergence of antimicrobial resistance.
Morganella has long flown under the radar of clinical microbiology, despite being a motile, facultatively anaerobic, Gram-negative rod that lives as a normal resident of the human, mammalian, and reptile gut. As an opportunistic pathogen, it has been implicated in sepsis, abscesses, purple urine bag syndrome, chorioamnionitis, and cellulitis. The organism carries intrinsic defenses that complicate treatment: it constitutively produces a cephalosporinase called DHA that inactivates ampicillin, amoxicillin, and most first- and second-generation cephalosporins, and its low-affinity penicillin-binding protein PBP-2 leaves it poorly susceptible to imipenem. Since 2017, third-generation cephalosporin-resistant Morganella has appeared on the World Health Organization’s Bacterial Pathogen Priority List, and the 2024 update categorized it as critical. With incidence under 100 cases per million population but mortality of roughly 5 to 10 percent, and with multidrug-resistant and extensively drug-resistant strains increasingly documented, researchers argue the pathogen can no longer be ignored.
The new study was made possible in part by a taxonomic upheaval. For decades the genus was divided into just two species, M. morganii and M. psychrotolerans, with two subspecies within M. morganii. But a comprehensive genomic analysis published in 2024 on an international strain collection proposed a revised taxonomy: M. sibonii was promoted to full species status, and M. morganii was split into the subspecies morganii and intermedius. That same analysis revealed dramatic genomic differences between the clinically relevant species, including a trehalose operon found only in M. sibonii, distinct type III and type VI secretion systems, and an intrinsic tetracycline resistance gene, tetD, present only in the M. sibonii core genome. Because no fast, accurate, and affordable method currently exists to distinguish M. morganii from M. sibonii in the clinic, and because MALDI-TOF mass spectrometry tools are only now catching up, the epidemiology and pathophysiology of these organisms remain poorly charted territory.
The type VI secretion system itself is one of the most remarkable structures in microbiology. Built from thirteen core conserved proteins, TssA through TssM, the apparatus assembles a membrane complex anchored in the cell envelope, a baseplate, and a needle-like spike tipped with a VgrG protein capped by a PAAR domain, all wrapped in a contractile sheath. When triggered by contact with a target cell, the sheath contracts explosively, propelling the Hcp-VgrG-PAAR spear through the envelope of the prey cell, delivering a payload of toxic effectors such as nucleases, amidases, hydrolases, and phospholipases. After firing, a TssH ATPase disassembles the sheath so the system can reload and fire again. Effectors come in two flavors, cargo effectors that bind non-covalently to the spike and specialized bifunctional effectors fused to spike components, and each toxin is typically paired with an immunity protein that protects the attacker from its own weapon. Since effectors often damage DNA, bacterial warfare of this kind can drive mutagenesis, and DNA released from lysed competitors can be scavenged and incorporated, potentially spreading resistance genes.
To map this battlefield across Morganella, the team performed whole-genome sequencing on all 293 isolates using Illumina technology, assembling reads with Shovill and SPAdes and validating population structure through core-genome phylogenetics built with Panaroo, MAFFT, and IQ-TREE, cross-checked against hierarchically clustered average nucleotide identity matrices. The collection included 228 M. morganii subsp. morganii, 39 M. morganii subsp. intermedius, and 26 M. sibonii, and 104 carbapenemase-producing strains carrying enzymes such as NDM-1, OXA-48, and KPC-2. T6SS clusters were detected and classified with the SecReT6 platform and manually curated with RAST annotations, with subtype assignment based on the sequence of the tssB gene, a validated phylogenetic marker. Effectors and immunity proteins were hunted down by examining the genes flanking vgrG loci, translating predicted proteins with BlastP, and probing their functions through NCBI and AlphaFold structural databases.
The headline result is a stark phylogenetic split in weaponry. Fully 92 percent of M. sibonii isolates carried four distinct T6SS clusters representing subtypes i1, i3 version 1, i3 version 2, and i5, with the remaining isolates carrying at least three. By contrast, 62.3 percent of M. morganii subsp. morganii genomes contained no T6SS at all, and the remaining 37.7 percent carried exactly one cluster, always of subtype i1. The newly recognized M. morganii subsp. intermedius fell in between, showing anywhere from zero to four clusters, with 46 percent of isolates carrying a single i5 cluster. Synteny analysis showed the structural gene arrangement was conserved across species and clusters occupied the same chromosomal loci, but recombination had clearly reshaped the landscape: in most T6SS-negative M. morganii subsp. morganii isolates, only a vestigial tssF gene remained at the ancestral i1 site, evidence of partial deletion rather than true absence. The two i3 versions in M. sibonii sit at different genomic locations, differ in gene content, and have phylogenetically distant tssB sequences, pointing to two independent acquisition events rather than a simple duplication. The i3 version 1 cluster sits just downstream of the trehalose operon and appears unique to M. sibonii.
The effector repertoires were equally divergent. Among M. morganii subsp. morganii strains, a single weapon dominated: the tseV gene, encoding a putative endonuclease of the VRR-NUC family, appeared in 95 percent of the 123 effectors identified, always paired with its cognate immunity protein TsiV. M. sibonii, by contrast, deployed a far more diverse arsenal, with putative lipases making up 35 percent of its predicted effectors and S-type pyocins, magnesium-dependent DNases known from Yersinia pseudotuberculosis, appearing in 13.5 percent of isolates with no accompanying immunity protein, hinting at a role in attacking eukaryotic cells. M. morganii subsp. intermedius blended traits from both relatives, carrying Rhs repeat-associated toxins in nearly half of its isolates alongside lipases, TseV, and the VasX membrane-depolarizing toxin otherwise absent from the genus. Rare finds included a polymorphic Ntox33 ribonuclease, a Tde1/Tdi1 toxin-immunity pair homologous to Agrobacterium tumefaciens DNase effectors, and a RelE/ParE toxin-antitoxin system. Sequence comparisons revealed highly conserved tseV variants, tseV_M1 in M. morganii and tseV_M2 in M. sibonii, while Rhs, lipase, and S-type pyocin genes showed much deeper divergence, partitioning into distinct species-associated groups.
The study also documented the distribution of vgrG genes, which encode the trimeric spike tip to which effectors attach and which can exist as orphan copies scattered around the genome. All 26 M. sibonii isolates were T6SS-positive and carried between one and six vgrG copies, while only 54 percent of M. morganii subsp. morganii isolates had even one. Most tellingly, M. morganii subsp. intermedius isolates harboring only the i5 subtype had no annotated vgrG genes at all, raising the question of whether those clusters can actually deliver effectors, whereas vgrG abundance tracked with the presence of i1 and i3 version 2 clusters, implicating subtype i1 as the primary effector-export workhorse. Chaperone and adaptor proteins, including Eag-family DUF1795 proteins and DUF2169-containing proteins that bridge VgrG to PAAR-capped effectors, were found almost exclusively in the two more heavily armed lineages.
Why would multidrug-resistant strains and heavily armed strains go hand in hand? The data showed a suggestive but statistically insignificant trend: 56.7 percent of carbapenemase producers carried at least one T6SS cluster versus 48.1 percent of non-producers. The authors point to a growing body of evidence that interbacterial competition and antimicrobial resistance are mechanistically intertwined. DNA-damaging effectors delivered during bacterial warfare can raise mutation rates, as demonstrated by the double-stranded DNA deaminase DddA of Burkholderia cenocepacia, which accelerates rifampicin resistance through rpoB mutations, while lipases and cell-wall hydrolases lyse competitors and release extracellular DNA that surviving bacteria can scavenge, resistance genes included. The remarkable multiplicity of toxins within M. sibonii, carrying up to four separate T6SS machines with distinct effector loads, may also limit the ability of competitors to evolve resistance, since defeating multiple independent weapons simultaneously is far harder than defeating one.
The researchers are candid about the limits of the work. SecReT6, the most comprehensive T6SS annotation platform available, relies on homology to previously characterized systems and may miss novel effectors, a bias the team partially offset with BLASTp searches against NCBI and AlphaFold. Most genomes were sequenced with short-read technology, which can truncate genes or incorrectly merge adjacent contigs, so annotations were cross-checked with RAST, and the authors note that long-read sequencing would sharpen cluster resolution. Discrepancies between Prokka and RAST in vgrG annotation further complicate the picture. Still, the study delivers the first panoramic view of the Morganella secretome, and it flags candidate effectors that could underpin both antibacterial dominance in crowded niches and anti-eukaryotic interactions with host tissues. The authors caution that every prediction now awaits confirmation in the wet lab: characterizing how each subtype is activated, what its effectors actually target, and how the corresponding immunity proteins work will be essential to understanding whether these molecular spearguns help explain why M. sibonii and M. morganii, so recently the same species on paper, behave so differently in the clinic.
Subject of Research: Distribution, diversity, and effector repertoire of the type VI secretion system (T6SS) in clinically relevant Morganella species, based on analysis of 293 whole-genome sequenced clinical isolates
Subject of Research: Biology
Article Title: Genome-Wide In Silico Analysis of the Type VI Secretion System (T6SS) Within the Morganella Genus
Article References: Duque, M., Jacquemin, A., Girlich, D., Bonnin, R. A., & Dortet, L. (2026). Genome‐Wide In Silico Analysis of the Type VI Secretion System (T6SS) Within the Morganella Genus. MicrobiologyOpen, 15(3), Article e70304. https://doi.org/10.1002/mbo3.70304
Image Credits: AI Generated
DOI: 10.1002/mbo3.70304
Keywords: Morganella, type VI secretion system, T6SS, M. sibonii, M. morganii, effectors, immunity proteins, bacterial warfare, antimicrobial resistance, whole-genome sequencing, WHO bacterial priority pathogens, carbapenemase producers
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Juliet Wilcox. (August 30, 2026). Genome-Wide Scan Reveals Type VI Secretion Systems Across Morganella Species. Scienmag. https://scienmag.com/genome-wide-scan-reveals-type-vi-secretion-systems-across-morganella-species/
Juliet Wilcox. “Genome-Wide Scan Reveals Type VI Secretion Systems Across Morganella Species.” Scienmag, 30 August 2026, https://scienmag.com/genome-wide-scan-reveals-type-vi-secretion-systems-across-morganella-species/. Accessed 30 August 2026.
Juliet Wilcox. “Genome-Wide Scan Reveals Type VI Secretion Systems Across Morganella Species.” Scienmag. August 30, 2026. https://scienmag.com/genome-wide-scan-reveals-type-vi-secretion-systems-across-morganella-species/
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