ORIGINAL PAPER A heterodimer comprised of two bovine lactoferrin antimicrobial peptides exhibits powerful bactericidal activity against Burkholderia pseudomallei Aekkalak Puknun • Jan G. M. Bolscher • Kamran Nazmi • Enno C. I. Veerman • Sumalee Tungpradabkul • Surasakdi Wongratanacheewin • Sakawrat Kanthawong • Suwimol Taweechaisupapong Received: 20 November 2012 / Accepted: 6 February 2013 / Published online: 13 February 2013 Ó Springer Science+Business Media Dordrecht 2013 Abstract Melioidosis is a severe infectious disease that is endemic in Southeast Asia and Northern Australia. Burk- holderia pseudomallei, the causative agent of this disease, has developed resistance to an increasing list of antibiotics, demanding a search for novel agents. Lactoferricin and lactoferrampin are two antimicrobial domains of lactoferrin with a broad spectrum of antimicrobial activity. A hybrid peptide (LFchimera) containing lactoferrampin (LFam- pin265–284) and a part of lactoferricin (LFcin17–30) has strikingly higher antimicrobial activities compared to the individual peptides. In this study, the antimicrobial activ- ities of this chimeric construct (LFchimera1), as well as of another one containing LFcin17–30 and LFampin268–284, a shorter fragment of LFampin265–284 (LFchimera2), and the constituent peptides were tested against 7 isolates of B. pseudomallei and compared to the preferential antibiotic ceftazidime (CAZ). All isolates including B. pseudomallei 979b shown to be resistant to CAZ, at a density of 10 5 CFU/ml, could be killed by 5–10 lM of LFchimera1 within 2 h, while the other peptides as well as the antibiotic CAZ only inhibited the B. pseudomallei strains resulting in an overgrowth in 24 h. These data indicate that LFchi- mera1 could be considered for development of therapeutic agents against B. pseudomallei. Keywords Antimicrobial activity Á Antimicrobial peptide Á Burkholderia pseudomallei Á Lactoferrin Á LFchimera Introduction Burkholderia pseudomallei is classified by the Centers for Disease Control and Prevention as a category B warfare agent (Rotz et al. 2002) and is the causative agent of meli- oidosis, a severe infectious disease with a wide range of clinical presentations. Melioidosis is highly endemic in Thailand and northern Australia; recently, however, meli- oidosis has been increasingly recognized in Central and South America (Inglis et al. 2006). With the increase in global travel by humans and global transport of animals, melioidosis is considered an emerging infectious disease. B. pseudomallei is intrinsically resistant to many of the cur- rently marketed antibiotics, which limits their therapeutic use during patient treatment (Chaowagul 2000). The current standard treatment with agents to which B. pseudomallei is susceptible requires 2–4 weeks of parenteral therapy e.g. with ceftazidime (CAZ) as initial intensive therapy, followed by 3–6 months of oral eradication therapy e.g. with trimethoprim/sulfamethoxazole, doxycycline, chloramphen- icol or a combination therapy. Despite this vigorous A. Puknun Á S. Wongratanacheewin Á S. Kanthawong Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand A. Puknun Á S. Wongratanacheewin Á S. Kanthawong Á S. Taweechaisupapong Melioidosis Research Center, Khon Kaen University, Khon Kaen 40002, Thailand J. G. M. Bolscher Á K. Nazmi Á E. C. I. Veerman Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU Universiteit Amsterdam, 1081 LA Amsterdam, The Netherlands S. Tungpradabkul Faculty of Science, Department of Biochemistry, Mahidol University, Bangkok 10400, Thailand S. Taweechaisupapong (&) Faculty of Dentistry, Department of Oral Diagnosis, Biofilm Research Group, Khon Kaen University, Khon Kaen 40002, Thailand e-mail: suvi_taw@kku.ac.th 123 World J Microbiol Biotechnol (2013) 29:1217–1224 DOI 10.1007/s11274-013-1284-6