# Molecular epidemiological association between antimicrobial resistance characteristics and type III secretion system in carbapenem-resistant Pseudomonas aeruginosa from lower respiratory tract infections **Authors:** Yun Zhou, Yanzi Chang, Chen Huang, Ximing Wang, Feng Wang, Hong Li PMC · DOI: 10.3389/fcimb.2026.1757868 · Frontiers in Cellular and Infection Microbiology · 2026-02-17 ## Abstract Objective: This study investigated the antimicrobial resistance profile of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and its association with the T3SS, aiming to provide evidence for managing highly resistant and virulent CRPA and to guide the optimization of infection control strategies. Retrospective cohort study was performed with CRPA lower respiratory tract infection from a tertiary hospital (July, 2021, and May, 2025). All strains underwent whole-genome sequencing (WGS), antimicrobial susceptibility testing(AST); selected isolates’ virulence were further evaluated using galleria mellonella infection assays. Among 106 patients caused by CRPA infections, the majority were male (73.6%), with a median age of 69.5 years and median hospital stay of 26.5 days. Prior antibiotic exposure included piperacillin/tazobactam (57.5%) and carbapenems (49.1%). AST revealed high resistance to piperacillin/tazobactam, but favorable susceptibility to ceftazidime/avibactam and tobramycin, with no polymyxin B resistance. Multidrug resistance occurred in 49.1% of isolates, and 28.3% were difficult-to-treat Pseudomonas aeruginosa (DTR-PA). The exoU and exoS genes were detected in 28.3% and 64.2% of strains, respectively, with 7.5% co-detection. ExoU+/exoS- strains showed significantly higher resistance to ceftazidime, cefepime, and piperacillin/tazobactam. All isolates had oprD mutations. Carbapenemase genes were found in 21.7%, primarily blaKPC-3.ExoU+/exoS- strains were linked to blaKPC-3 and blaOXA-50 subtypes(OXA-488,OXA-1032), while exoU-/exoS+ strains associated with blaOXA-486 and blaOXA-904. Among 59 sequence types, ST1076 (13.2%) and ST491 (10.4%) dominated, with serotypes O11 (38.7%) and O6 (25.5%) prevalent. Six international high-risk clones included ST233, ST244, and ST357. Phylogenetically, phylogroup A (exoU-/exoS+, e.g., PAO1) was larger, and phylogroup B (exoU+/exoS-, e.g., PA14) included highly virulent strains. ExoU+/exoS- strains grouped in ST1076 and ST357, and exoU+/exoS+ in ST463. The survival of galleria mellonella further indicated that carrying the exoU may cause a higher lethality rate. ExoU+/exoS- strains were strongly associated with resistance genes like blaKPC-3,blaOXA-488, blaOXA-1032, ICU admission and exhibited a more pronounced drug-resistant phenotype. Potential high-risk clones such as ST1076-O11 and ST463-O4 display both extensive resistance and high virulence, underscoring the clinical and public health importance of enhanced surveillance and effective containment. ## Full-text entities - **Genes:** KPC2 [NCBI Gene 16834582], PEX13 (peroxisomal biogenesis factor 13) [NCBI Gene 5194] {aka NALD, PBD11A, PBD11B, ZWS}, exoS (exoenzyme S) [NCBI Gene 879837], OPRD1 (opioid receptor delta 1) [NCBI Gene 4985] {aka DOP, DOR, DOR1, OPRD}, beta-lactamase [NCBI Gene 4290808] - **Diseases:** respirary tract infection (MESH:D012141), pneumonia (MESH:D011014), drug resistance (MESH:D000069279), CRPA (MESH:D011552), KPC (MESH:C565455), death (MESH:D003643), infected (MESH:D007239), Toxicity (MESH:D064420) - **Chemicals:** O (MESH:D010100), aminoglycosides (MESH:D000617), ciprofloxacin (MESH:D002939), avibactam (MESH:C543519), levofloxacin (MESH:D064704), meropenem (MESH:D000077731), cefepime (MESH:D000077723), ceftazidime (MESH:D002442), Carbapenem (MESH:D015780), tobramycin (MESH:D014031), insulin (MESH:D007328), OXA-488 (-), fosfomycin (MESH:D005578), imipenem-cilastatin (MESH:D000077728), CZA (MESH:C000595613), aztreonam (MESH:D001398), piperacillin-tazobactam (MESH:D000077725), Amino acid (MESH:D000596), cephalosporins (MESH:D002511), fluoroquinolones (MESH:D024841), imipenem (MESH:D015378), LPS (MESH:D008070), beta-lactams (MESH:D047090), cefoperazone (MESH:D002438), chloramphenicol (MESH:D002701) - **Species:** Pseudomonas aeruginosa PA14 (strain) [taxon 652611], HL [taxon 2008771], Pseudomonas aeruginosa (species) [taxon 287], Pseudomonas aeruginosa PAO1 (strain) [taxon 208964], Escherichia coli ATCC 8739 (strain) [taxon 481805], Galleria mellonella (greater wax moth, species) [taxon 7137], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Escherichia coli ATCC 25922 (strain) [taxon 1322345] - **Mutations:** Ala281Gly, Glu202Gln, Val42fs, Ala267Ser, Val127fs, Asp43Asn, Lys44fs, Gly425Ala, Phe148fs, Arg234fs, Gly106Asp, Lys115Thr, Gln301Glu, D179Y, Thr161fs, Gly132del, Leu292fs, Gly314fs, Leu102fs, Glu230Lys, Lys296Gln, Thr72fs, Asn262Thr, Gly162fs, Phe69Val, Ala116del, Thr103Ser, Asn107fs, Gly41fs, Glu27fs, Thr181fs, Thr203fs, Gly151fs, Ile210Ala, Ala315Gly, Phe170Leu, Gln424Glu, Thr276Ala, Asn700fs, Ser57fs, Pro405fs, Met111fs, Ser223fs, Arg342fs, Ala15fs, Leu123fs, Val127Leu, Val151fs, Ser240Thr, Ser278Pro, Gln158fs, Val352fs, Val189Thr, Thr188fs, Glu140fs, Gln402fs, Ile15fs, Ser59fs, Leu224fs, Ter444Ter - **Cell lines:** PAO1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12953427/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953427/full.md ## References 55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12953427/full.md --- Source: https://tomesphere.com/paper/PMC12953427