Acinetobacter baumannii causes multidrug resistance, leading to fatal infections in humans. In this study, we showed that Lys AB2 P3-His-a hexahistidine-tagged form of an antimicrobial peptide (AMP) loaded onto DNA aptamer-functionalized gold nanoparticles (AuNP-Apt)-can effectively inhibit A. baumannii infection in mice. When A. baumannii-infected mice were intraperitoneally injected with AuNP-Apt loaded with Lys AB2 P3-His, a marked reduction in A. baumannii colonization was observed in the mouse organs, leading to prominently increased survival time and rate of the mice compared to those of the control mice treated with AuNP-Apt or Lys AB2 P3-His only. This study shows that AMPs loaded onto AuNP-Apt could be an effective therapeutic tool against infections caused by multidrug-resistant pathogenic bacteria in humans.
Almaaytah, A., Mohammed, G.K., Abualhaijaa, A., and Al-Balas, Q. 2017. Development of novel ultrashort antimicrobial peptide nanoparticles with potent antimicrobial and antibiofilm activities against multidrug-resistant bacteria. Drug Des. Devel. Ther. 11, 3159–3170.
[PMID: 29138537]
Bassetti, M., Ginocchio, F., and Mikulska, M. 2011 New treatment options against Gram-negative organisms. In Vincent, J.L. (ed.), Annual Update in Intensive Care and Emergency Medicine 2011, vol. 1. Springer, Berlin, Germany.
Bergogne-Bérézin, E. and Towner, K.J. 1996. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin. Microbiol. Rev. 9, 148–165.
[PMID: 8964033]
Blot, S., Vandewoude, K., and Colardyn, F. 2003. Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study. Intensive Care Med. 29, 471–475.
[PMID: 12577148]
Carratalá, J.V., Serna, N., Villaverde, A., Vázquez, E., and Ferrer-Miralles, N. 2020. Nanostructured antimicrobial peptides: the last push towards clinics. Biotechnol. Adv. 44, 107603.
[PMID: 32738381]
Cerqueira, G.M. and Peleg, A.Y. 2011. Insights into Acinetobacter baumannii pathogenicity. IUBMB Life 63, 1055–1060.
[PMID: 21989983]
Cheng, M.M.C., Cuda, G., Bunimovich, Y.L., Gaspari, M., Heath, J.R., Hill, H.D., Mirkin, C.A., Nijdam, A.J., Terracciano, R., Thundat, T., et al. 2006. Nanotechnologies for biomolecular detection and medical diagnostics. Curr. Opin. Chem. Biol. 10, 11–19.
[PMID: 16418011]
Choi, J., Baek, J., Kweon, D., Ko, K.S., and Yoon, H. 2020. Rapid determination of carbapenem resistance by low-cost colorimetric methods: propidium Iodide and alamar blue staining. J. Microbiol. 58, 415–421.
[PMID: 32221821]
Choi, C.H., Lee, J.S., Lee, Y.C., Park, T.I., and Lee, J.C. 2008. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol. 8, 216.
[PMID: 19068136]
Connor, E.E., Mwamuka, J., Gole, A., Murphy, C.J., and Wyatt, M.D. 2005. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1, 325–327.
[PMID: 17193451]
Darouiche, R.O. and Hamill, R.J. 1994. Antibiotic penetration of and bactericidal activity within endothelial cells. Antimicrob. Agents Chemother. 38, 1059–1064.
[PMID: 8067738]
De Vegas, E.Z.S., Nieves, B., Araque, M., Velasco, E., Ruíz, J., and Vila, J. 2006. Outbreak of infection with Acinetobacter strain RUH 1139 in an intensive care unit. Infect. Control Hosp. Epidemiol. 27, 397–403.
[PMID: 16622819]
Dijkshoorn, L., Nemec, A., and Seifert, H. 2007. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat. Rev. Microbiol. 5, 939–951.
[PMID: 18007677]
Esposito, S., Tagliabue, C., Bosis, S., and Principi, N. 2011. Levofloxacin for the treatment of Mycoplasma pneumoniae-associated meningoencephalitis in childhood. Int. J. Antimicrob. Agents 37, 472–475.
[PMID: 21377335]
Fagon, J.Y., Chastre, J., Domart, Y., Trouillet, J.L., and Gibert, C. 1996. Mortality due to ventilator-associated pneumonia or colonization with Pseudomonas or Acinetobacter species: assessment by quantitative culture of samples obtained by a protected specimen brush. Clin. Infect. Dis. 23, 538–542.
[PMID: 8879777]
Fair, R.J. and Tor, Y. 2014. Antibiotics and bacterial resistance in the 21st century. Perspect. Medicin. Chem. 6, 25–64.
[PMID: 25232278]
Gaddy, J.A., Tomaras, A.P., and Actis, L.A. 2009. The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells. Infect. Immun. 77, 3150–3160.
[PMID: 19470746]
Garnacho-Montero, J., Ortiz-Leyba, C., Jiménez-Jiménez, F., Barrero-Almódovar, A., García-Garmendia, J., Bernabeu-Wittell, M., Gallego-Lara, S., and Madrazo-Osuna, J. 2003. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin. Infect. Dis. 36, 1111–1118.
[PMID: 12715304]
Gentilucci, L., Tolomelli, A., and Squassabia, F. 2006. Peptides and peptidomimetics in medicine, surgery and biotechnology. Curr. Med. Chem. 13, 2449–2466.
[PMID: 16918365]
Hancock, R.E.W. and Sahl, H.G. 2006. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 24, 1551–1557.
[PMID: 17160061]
Jawad, A., Seifert, H., Snelling, A., Heritage, J., and Hawkey, P.M. 1998. Survival of Acinetobacter baumannii on dry surfaces: comparison of outbreak and sporadic isolates. J. Clin. Microbiol. 36, 1938–1941.
[PMID: 9650940]
Jiang, Q., Lou, Z., Wang, H., and Chen, C. 2019. Antimicrobial effect and proposed action mechanism of cordycepin against Escherichia coli and Bacillus subtilis. J. Microbiol. 57, 288–297.
[PMID: 30929229]
Kang, H.K., Kim, C., Seo, C.H., and Park, Y. 2017. The therapeutic applications of antimicrobial peptides (AMPs): a patent review. J. Microbiol. 55, 1–12.
[PMID: 28035594]
Kang, S.J., Park, S.J., Mishig-Ochir, T., and Lee, B.J. 2014. Antimicrobial peptides: therapeutic potentials. Expert Rev. Anti Infect. Ther. 12, 1477–1486.
[PMID: 25371141]
Kim, S.M., Escorbar, I., Lee, K., Fuchs, B.B., Mylonakis, E., and Kim, W. 2020. Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening. J. Microbiol. 58, 431–444.
[PMID: 32462486]
Kim, S.Y., Park, C., Jang, H.J., Kim, B.O., Bae, H.W., Chung, I.Y., Kim, E.S., and Cho, Y.H. 2019. Antibacterial strategies inspired by the oxidative stress and response networks. J. Microbiol. 57, 203–212.
[PMID: 30806977]
Kim, M., Park, J., Kang, M., Yang, J., and Park, W. 2021. Gain and loss of antibiotic resistant genes in multidrug resistant bacteria: One Health perspective. J. Microbiol. 59, 535–545.
[PMID: 33877574]
Ko, K.S. 2019. Antibiotic-resistant clones in Gram-negative pathogens: presence of global clones in Korea. J. Microbiol. 57, 195–202.
[PMID: 30552629]
Kökpinar, Ö., Walter, J.G., Shoham, Y., Stahl, F., and Scheper, T. 2011. Aptamer-based downstream processing of his-tagged proteins utilizing magnetic beads. Biotechnol. Bioeng. 108, 2371–2379.
[PMID: 21538335]
Kramer, A., Schwebke, I., and Kampf, G. 2006. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect. Dis. 6, 130.
[PMID: 16914034]
Lai, M.J., Lin, N.T., Hu, A., Soo, P.C., Chen, L.K., Chen, L.H., and Chang, K.C. 2011. Antibacterial activity of Acinetobacter baumannii phage φAB2 endolysin (LysAB2) against both Grampositive and Gram-negative bacteria. Appl. Microbiol. Biotechnol. 90, 529–539.
[PMID: 21264466]
Lee, K., Kim, D.W., and Cha, C.J. 2021. Overview of bioinformatic methods for analysis of antibiotic resistome from genome and metagenome data. J. Microbiol. 59, 270–280.
[PMID: 33624264]
Lee, H.T., Kim, S.K., and Yoon, J.W. 2019. Antisense peptide nucleic acids as a potential anti-infective agent. J. Microbiol. 57, 423–430.
[PMID: 31054136]
Lee, B., Park, J., Ryu, M., Kim, S., Joo, M., Yeom, J.H., Kim, S., Park, Y., Lee, K., and Bae, J. 2017. Antimicrobial peptide-loaded gold nanoparticle-DNA aptamer conjugates as highly effective antibacterial therapeutics against Vibrio vulnificus. Sci. Rep. 7, 13572.
[PMID: 29051620]
Lehar, S.M., Pillow, T., Xu, M., Staben, L., Kajihara, K.K., Vandlen, R., DePalatis, L., Raab, H., Hazenbos, W.L., Morisaki, J.H., et al. 2015. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323–328.
[PMID: 26536114]
Lemon, D.J., Kay, M.K., Titus, J.K., Ford, A.A., Chen, W., Hamlin, N.J., and Hwang, Y.Y. 2019. Construction of a genetically modified T7Select phage system to express the antimicrobial peptide 1018. J. Microbiol. 57, 532–538.
[PMID: 31054139]
Mahgoub, S., Ahmed, J., and Glatt, A.E. 2002. Underlying characteristics of patients harboring highly resistant Acinetobacter baumannii. Am. J. Infect. Control 30, 386–390.
[PMID: 12410214]
Makabenta, J.M.V., Nabawy, A., Li, C.H., Schmidt-Malan, S., Patel, R., and Rotello, V.M. 2021. Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nat. Rev. Microbiol. 19, 23–36.
[PMID: 32814862]
Marr, A.K., Gooderham, W.J., and Hancock, R.E. 2006. Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr. Opin. Pharmacol. 6, 468–472.
[PMID: 16890021]
McConnell, M.J., Domínguez-Herrera, J., Smani, Y., López-Rojas, R., Docobo-Pérez, F., and Pachón, J. 2011. Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii. Infect. Immun. 79, 518–526.
[PMID: 20974823]
Mishra, B., Reiling, S., Zarena, D., and Wang, G. 2017. Host defense antimicrobial peptides as antibiotics: design and application strategies. Curr. Opin. Chem. Biol. 38, 87–96.
[PMID: 28399505]
Mukhopadhyay, S., Prasad, A.S.B., Mehta, C.H., and Nayak, U.Y. 2020. Antimicrobial peptide polymers: No escape to ESKAPE pathogens-a review. World J. Microbiol. Biotechnol. 36, 131.
[PMID: 32737599]
Nordström, R. and Malmsten, M. 2017. Delivery systems for antimicrobial peptides. Adv. Colloid Interface Sci. 242, 17–34.
[PMID: 28159168]
Paleos, C.M., Tsiourvas, D., Sideratou, Z., and Tziveleka, L. 2004. Acid-and salt-triggered multifunctional poly (propylene imine) dendrimer as a prospective drug delivery system. Biomacromolecules 5, 524–529.
[PMID: 15003016]
Park, Y.K., Lee, G.H., Baek, J.Y., Chung, D.R., Peck, K.R., Song, J.H., and Ko, K.S. 2010. A single clone of Acinetobacter baumannii, ST22, is responsible for high antimicrobial resistance rates of Acinetobacter spp. isolates that cause bacteremia and urinary tract infections in Korea. Microb. Drug Resist. 16, 143–149.
[PMID: 20370437]
Parra-Millán, R., Guerrero-Gómez, D., Ayerbe-Algaba, R., Pachón-Ibáñez, M.E., Miranda-Vizuete, A., Pachón, J., and Smani, Y. 2018. Intracellular trafficking and persistence of Acinetobacter baumannii requires transcription factor EB. mSphere 3, e00106–18.
[PMID: 29600279]
Peleg, A.Y., Seifert, H., and Paterson, D.L. 2008. Acinetobacter baumannii: emergence of a successful pathogen. Clin. Microbiol. Rev. 21, 538–582.
[PMID: 18625687]
Perez, F., Hujer, A.M., Hujer, K.M., Decker, B.K., Rather, P.N., and Bonomo, R.A. 2007. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51, 3471–3484.
[PMID: 17646423]
Projan, S.J. 2003. Why is big Pharma getting out of antibacterial drug discovery? Curr. Opin. Microbiol. 6, 427–430.
[PMID: 14572532]
Qiu, H., KuoLee, R., Harris, G., Van Rooijen, N., Patel, G.B., and Chen, W. 2012. Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection. PLoS ONE 7, e40019.
[PMID: 22768201]
Rice, L.B. 2008. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. The University of Chicago Press. Chicago, Illinois, USA.
Rolain, J.M., Diene, S.M., Kempf, M., Gimenez, G., Robert, C., and Raoult, D. 2013. Real-time sequencing to decipher the molecular mechanism of resistance of a clinical pan-drug-resistant Acinetobacter baumannii isolate from Marseille, France. Antimicrob. Agents Chemother. 57, 592–596.
[PMID: 23070160]
Roscia, G., Falciani, C., Bracci, L., and Pini, A. 2013. The development of antimicrobial peptides as new antibacterial drugs. Curr. Protein Pept. Sci. 14, 641–649.
[PMID: 24384032]
Rosi, N.L. and Mirkin, C.A. 2005. Nanostructures in biodiagnostics. Chem. Rev. 105, 1547–1562.
[PMID: 15826019]
Ryu, M., Park, J., Yeom, J.H., Joo, M., and Lee, K. 2021. Rediscovery of antimicrobial peptides as therapeutic agents. J. Microbiol. 59, 113–123.
[PMID: 33527313]
Schmid, G. 1992. Large clusters and colloids. Metals in the embryonic state. Chem. Rev. 92, 1709–1727.
Shin, B. and Park, W. 2017. Antibiotic resistance of pathogenic Acinetobacter species and emerging combination therapy. J. Microbiol. 55, 837–849.
[PMID: 29076065]
Theaker, C., Azadian, B., and Soni, N. 2003. The impact of Acinetobacter baumannii in the intensive care unit. Anaesthesia 58, 271–274.
[PMID: 12638567]
Valero, C., Palomo, J.D.G., Matorras, P., Fernández-Mazarrasa, C., Fernández, C.G., and Fariñas, M.C. 2001. Acinetobacter bacteraemia in a teaching hospital, 1989–1998. Eur. J. Intern. Med. 12, 425–429.
[PMID: 11557328]
Wang, S.H., Sheng, W.H., Chang, Y.Y., Wang, L.H., Lin, H.C., Chen, M.L., Pan, H.J., Ko, W.J., Chang, S.C., and Lin, F.Y. 2003. Healthcare-associated outbreak due to pan-drug resistant Acinetobacter baumannii in a surgical intensive care unit. J. Hosp. Infect. 53, 97–102.
[PMID: 12586567]
Wróblewska, M. 2006. Novel therapies of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp. infections: the state of the art. Arch. Immunol. Ther. Exp. 54, 113–120.
Xiong, M.H., Bao, Y., Yang, X.Z., Zhu, Y.H., and Wang, J. 2014. Delivery of antibiotics with polymeric particles. Adv. Drug Deliv. Rev. 78, 63–76.
[PMID: 24548540]
Yeom, J.H., Lee, B., Kim, D., Lee, J., Kim, S., Bae, J., Park, Y., and Lee, K. 2016. Gold nanoparticle-DNA aptamer conjugate-assisted delivery of antimicrobial peptide effectively eliminates intra-cellular Salmonella enterica serovar Typhimurium. Biomaterials 104, 43–51.
[PMID: 27424215]
Yeung, A.T.Y., Gellatly, S.L., and Hancock, R.E. 2011. Multifunctional cationic host defence peptides and their clinical applications. Cell. Mol. Life Sci. 68, 2161.
[PMID: 21573784]