{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:00Z","timestamp":1785422700052,"version":"3.56.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN 04210-2020"],"award-info":[{"award-number":["RGPIN 04210-2020"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RGPIN 04210-2020"],"award-info":[{"award-number":["RGPIN 04210-2020"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008459","name":"University of Calgary","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008459","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03yjb2x39","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cationic antimicrobial peptides (AMPs) that can target multidrug-resistant pathogenic bacteria via multiple mechanisms are considered promising alternatives to antibiotics. Small (~9 kDa) highly acidic acyl carrier proteins (ACPs), which are a well-known cofactor protein in bacterial fatty acid synthesis (FAS), are a potential intracellular target for AMPs. A previous study has demonstrated that the human AMP LL-37 can bind to ACP and thereby affect FAS and the bacterial membrane integrity. In this work, we have investigated the interactions of different classes of AMPs and antibiofilm peptides (ABPs) with the ACPs of two pathogens. We first studied the folding characteristics of the two ACPs and found that Pseudomonas aeruginosa ACP (PaACP) is fully folded at neutral pH in the absence of divalent cations. On the other hand, the homologous Francisella novicida ACP (FnACP) is unfolded at low ionic strength, but it adopts a fully folded conformation after the addition of divalent cations such as Ca2+ or Mg2+. These distinct characteristics were shown to be related to a unique His residue that is involved in a stabilizing cation\u2013\u03c0 interaction. Subsequent biophysical SPR and NMR interaction studies reveal that cationic AMPs and ABPs such as LL-37, melittin, tritrpticin, indolicidin, puroindoline A, lactoferricin B and IDR-1018, but not F5W-magainin 2, can bind to both apo- and holo-ACPs. Binding of Arg-rich peptides is preferred over their Lys-rich analogs. Interestingly, all the peptides bind to holo-ACP with higher affinity than to apo-ACP, which lacks the functionally important phosphopantothenate group. NMR peak intensity perturbation data reveal that helix II of ACP, which is known to be directly involved in complex formation with bacterial FAS enzymes, acts as a common and main recognition site for the peptides. We propose that binding of AMPs and ABPs to this region of bacterial ACPs can directly block fatty acid synthesis and interfere in other ACP-dependent biosynthetic and regulatory events, which in turn could contribute to killing the bacteria and could also intervene in biofilm formation.<\/jats:p>","DOI":"10.3390\/ijms27114823","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"4823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacterial Acyl Carrier Proteins Are a Cytoplasmic Target for Different Cationic Antimicrobial and Antibiofilm Peptides"],"prefix":"10.3390","volume":"27","author":[{"given":"Gopal","family":"Ramamourthy","sequence":"first","affiliation":[{"name":"Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4107-9264","authenticated-orcid":false,"given":"Subrata","family":"Paul","sequence":"additional","affiliation":[{"name":"Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7954-9757","authenticated-orcid":false,"given":"Ishrat M.","family":"Jalal","sequence":"additional","affiliation":[{"name":"Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The expanding scope of antimicrobial peptide structures and their modes of action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/bip.22250","article-title":"Peptide design for antimicrobial and immunomodulatory applications","volume":"100","author":"Haney","year":"2013","journal-title":"Biopolymers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21037\/atm.2016.09.14","article-title":"Resistance mechanisms","volume":"4","author":"Cag","year":"2016","journal-title":"Ann. 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