Characteristics of rare ST463 carbapenem-resistant Pseudomonas aeruginosa clinical isolates from blood

Zhang, Xiaodong; Tang, Miran; Xu, Ye; Xu, Mengxin; Qian, Changrui; Zheng, Xiangkuo; Zhou, Tieli; Wu, Qingping

doi:10.1016/j.jgar.2023.01.011

Cited by 4 publications

(2 citation statements)

References 24 publications

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“…9 ST463 is the predominant strain in cases of bloodstream infection caused by CRPA, accounting for CRPA is significantly higher compared to non-ST463 CRPA. 11 Bla AFM-1 CRPA strains are relatively rare. In 2018, a subclass B1b (Metallo-b-lactamase) (MBL) was recognized in an Alcaligenes faecalis strain and named AFM-1.…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

Shen,

Cao,

et al. 2024

IDR

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Background Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam . The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa . Case Presentation The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes bla AFM-1 and bla KPC-2 , which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B , surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up. Conclusion This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.

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Section: Discussionmentioning

confidence: 99%

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

Shen,

Cao,

et al. 2024

IDR

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“…The surveillance of KPC-producing P. aeruginosa isolates from different geographic regions in China showed that ST463 ( n = 107, 70.9%) was the main CRPA clone in East China ( 17 ). A recent study reported that ST463 P. aeruginosa is closely associated with blaKPC-2 and exoU and is spreading rapidly ( 18 ). A retrospective cohort study demonstrated that the mortality rates of the ST463 CRPA bloodstream infections (BSIs) were higher than those in the non-ST463 CRPA BSI, and the emergence and spread of the ST463 CRPA clone harboring the exoU gene in East China pose a new threat in the clinic ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

The type III secretion system facilitates systemic infections of Pseudomonas aeruginosa in the clinic

Wu,

Zhang,

et al. 2024

Microbiol Spectr

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Pseudomonas aeruginosa is a major opportunistic pathogen that can cause severe systemic infections. Here, we found that the type III secretion system effector ExoU was the main determinant of pathogenicity of a highly virulent clinical isolate strain, BSI_S5, of P. aeruginosa , which caused severe bloodstream infections and belongs to ST463/O4. Deletion of exoU showed significantly attenuated cytotoxicity and virulence in vivo , while deletion of two other unique genes from strain BSI_S5, chr_1696 and chr_4238 , which encodes type I secretion system permease/ATPase or polysaccharide biosynthesis protein, respectively, caused no apparent loss of toxicity compared to the parent strain, and complementation of the ΔexoU mutant restored its virulence. The presence of ExoU-induced lung lesions and the mucosal damage of gallbladder in mice, and the replication of the ΔexoU mutant was hindered in vivo compared with the parent strain. We show here for the first time that a clinical isolate with intact exoU harbored a mutation of T→G substitution in the adjacent specific Pseudomonas chaperone for ExoU ( spcU ), which caused phenylalanine to valine change at amino acid 94 of SpcU, resulting in significant loss of cytotoxicity. This finding suggests that intact exoU is not sufficient for cytotoxicity, but a functional downstream SpcU is required for ExoU secretion and cytotoxicity. Finally, we found that BSI_S5 harbored two types of insertion sequences adjacent to exoU , suggesting the potential of exoU to be transferred to other strains. Our study opens an avenue for further mechanistic study of P. aeruginosa systemic infections regarding its high pathogenicity and clinical spread. IMPORTANCE The identification of decisive virulence-associated genes in highly pathogenic P. aeruginosa isolates in the clinic is essential for diagnosis and the start of appropriate treatment. Over the past decades, P. aeruginosa ST463 has spread rapidly in East China and is highly resistant to β-lactams. Given the poor clinical outcome caused by this phenotype, detailed information regarding its decisive virulence genes and factors affecting virulence expression needs to be deciphered. Here, we demonstrate that the T3SS effector ExoU has toxic effects on mammalian cells and is required for virulence in the murine bloodstream infection model. Moreover, a functional downstream SpcU is required for ExoU secretion and cytotoxicity. This work highlights the potential role of ExoU in the pathogenesis of disease and provides a new perspective for further research on the development of new antimicrobials with antivirulence ability.

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Amikacin/Levofloxacin

2024

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Characteristics of rare ST463 carbapenem-resistant Pseudomonas aeruginosa clinical isolates from blood

Cited by 4 publications

References 24 publications

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

The type III secretion system facilitates systemic infections of Pseudomonas aeruginosa in the clinic

Amikacin/Levofloxacin

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