Scientific REPORTS | 7: 16580 | DOI:10.1038/s41598-017-16784-6
Macropis fulvipes Venom
component Macropin Exerts its
Antibacterial and Anti-Biolm
Properties by Damaging the Plasma
Membranes of Drug Resistant
Su Jin Ko
, Min Kyung Kim
, Jeong Kyu Bang
, Chang Ho Seo
, Tudor Luchian
The abuse of antibiotics for disease treatment has led to the emergence of multidrug resistant bacteria.
Antimicrobial peptides, found naturally in various organisms, have received increasing interest as
alternatives to conventional antibiotics because of their broad spectrum antimicrobial activity and low
cytotoxicity. In a previous report, Macropin, isolated from bee venom, exhibited antimicrobial activity
against both gram-positive and negative bacteria. In the present study, Macropin was synthesized and
its antibacterial and anti-biolm activities were tested against bacterial strains, including gram-positive
and negative bacteria, and drug resistant bacteria. Moreover, Macropin did not exhibit hemolytic
activity and cytotoxicity to keratinocytes, whereas Melittin, as a positive control, showed very high
toxicity. Circular dichroism assays showed that Macropin has an α-helical structure in membrane
mimic environments. Macropin binds to peptidoglycan and lipopolysaccharide and kills the bacteria
by disrupting their membranes. Moreover, the fractional inhibitory concentration index indicated
that Macropin has additive and partially synergistic eects with conventional antibiotics against drug
resistant bacteria. Thus, our study suggested that Macropin has potential for use of an antimicrobial
agent for infectious bacteria, including drug resistant bacteria.
Since the discovery of penicillin, many antibiotics have been developed and used to treat infectious diseases
caused by bacteria. Antibiotics kill bacteria by inhibiting cell wall synthesis, protein synthesis, or DNA synthesis.
When an antibiotic is used in the clinic, consideration should be given to characteristics such as the antimicro-
bial range and mechanism of action. Nonetheless, the indiscriminate use of antibiotics has resulted in bacteria
developing resistance to antibiotics. e number of resistant bacterial strains has increased, and some bacteria,
referred to as superbugs, have emerged with resistance to most antibiotics, thus posing a serious health risk
erefore, there is a need to develop new drugs that are less likely to induce resistance to treat drug-resistant
bacteria. Possible alternatives to conventional antibiotics are antimicrobial peptides (AMPs), which are part of
the innate immune response
. AMPs have a broad spectrum of antimicrobial activity against bacteria, including
multidrug resistant bacteria.
Generally, AMPs are found in nature and participate in host defense. AMPs are small proteins of between
12 and 50 amino acid residues. e secondary structures of AMPs include α-helices, β-sheets, extended struc-
tures, and loops
. In addition, AMPs tend to be amphipathic; i.e., they contain both hydrophilic and hydrophobic
Department of Biomedical Science, Chosun University, Gwangju, 61452, Korea.
Division of Magnetic Resonance,
Korea Basic Science Institute, Ochang, Chung-Buk, 363-883, Republic of Korea.
Department of Bioinformatics,
Kongju National University, Kongju, 314-701, South Korea.
Department of Physics, Alexandru I. Cuza University, Iasi,
Research Center for Proteineous Materials, Chosun University, Gwangju, 61452, Korea. Correspondence
and requests for materials should be addressed to T.L. (email: firstname.lastname@example.org) or Y.P. (email: email@example.com)
Received: 6 March 2017
Accepted: 14 November 2017
Published: xx xx xxxx