OXA β-lactamases from Acinetobacter spp. are membrane bound and secreted into outer membrane vesicles

被引:0
作者
Capodimonte, Lucia [1 ,2 ]
Meireles, Fernando Teixeira Pinto [3 ]
Bahr, Guillermo [1 ,2 ]
Bonomo, Robert A. [4 ,5 ,6 ,7 ,8 ,9 ,10 ]
Dal Peraro, Matteo [3 ]
Lopez, Carolina [1 ]
Vila, Alejandro J. [1 ,2 ,10 ]
机构
[1] CONICET IBR UNR, Inst Biol Mol & Celular Rosario, Rosario, Argentina
[2] Univ Nacl Rosario, Fac Ciencias Bioquim & Farmaceut, Area Biofis, Rosario, Santa Fe, Argentina
[3] Ecole Polytech Fed Lausanne EPFL, Inst Bioengn, Sch Life Sci, Lausanne, Switzerland
[4] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH USA
[5] Louis Stokes Vet Affairs Med Ctr, Res Serv, Cleveland, OH USA
[6] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH USA
[7] Case Western Reserve Univ, Dept Biochem, Sch Med, Cleveland, OH USA
[8] Case Western Reserve Univ, Dept Prote, Sch Med, Cleveland, OH USA
[9] Case Western Reserve Univ, Dept Bioinformat, Sch Med, Cleveland, OH USA
[10] CWRU Cleveland VAMC Ctr Antimicrobial Resistance, Case VA Cares, Cleveland, OH 44106 USA
基金
美国国家卫生研究院; 瑞士国家科学基金会;
关键词
lipidated beta-lactamases; OXA beta-lactamases; Acinetobacter spp; outer membrane vesicles; dissemination of antimicrobial resistance; BACTERIAL LIPOPROTEINS; CO-COLONIZATION; BAUMANNII; RESISTANCE; DATABASE; DISSEMINATION; MECHANISM; SYSTEM; FIELD; GENE;
D O I
10.1128/mbio.03343-24
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
beta-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced beta-lactamases was performed that revealed a predominance of putative lipidated enzymes in the Class D OXAs. Namely, 60% of the OXA Class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with beta-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (>99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from A. baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli, and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound beta-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated beta-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them.
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页数:19
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