Review
Biochemistry & Molecular Biology
Kornelius Zeth, Enea Sancho-Vaello
Summary: The human cathelicidin LL-37 is a versatile peptide with antimicrobial activity, playing a crucial role in targeting microorganisms. Recent structural studies have revealed the diversity and adaptability of LL-37 in interacting with lipid-like molecules. Complexes of LL-37 with detergents provide insights into mimicking lipids and inducing oligomerization and fibrillation, opening avenues for designing LL-37-derived peptides with enhanced antibiotic properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Floriana Cappiello, Sudhir Verma, Xiao Lin, Isabel Y. Moreno, Bruno Casciaro, Debarun Dutta, Alison M. McDermott, Mark Willcox, Vivien J. Coulson-Thomas, Maria Luisa Mangoni
Summary: The corneal epithelium is essential for both vision and immune defense. Corneal abrasion can lead to severe eye infections, but recent research has discovered peptides that not only treat keratitis but also promote corneal wound healing, which could have potential clinical applications.
Article
Infectious Diseases
Kylen E. Ridyard, Mariam Elsawy, Destina Mattrasingh, Darien Klein, Janine Strehmel, Carole Beaulieu, Alex Wong, Joerg Overhage
Summary: The rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. In this study, the synergy between the antimicrobial peptide LL-37 and various antibiotics was investigated against Escherichia coli and Pseudomonas aeruginosa strains. The combination of LL-37 and polymyxin B (PMB) showed strong synergy in preventing biofilm formation and eradicating pre-grown biofilms of E. coli and P. aeruginosa.
Article
Microbiology
Gladys Pinilla, Yenifer Tatiana Coronado, Gabriel Chaves, Liliana Munoz, Jeannette Navarrete, Luz Mary Salazar, Carlos Pelleschi Taborda, Julian E. Munoz
Summary: Fungal infections have become a major problem in immunosuppressed or ICU patients, and the resistance of fungi to conventional antifungal treatments is increasing. This study evaluated the in vitro antifungal activity of LL-37 analogue peptides against Candida spp. The results suggest that LL37-1 and AC-2 have the best inhibitory effect on Candida strains.
Article
Biochemical Research Methods
William F. Porto, Sergio A. Alencar
Summary: Cathelicidin antimicrobial peptides, including LL-37, are important host defense peptides with various activities. We investigated the effects of single nucleotide polymorphism (SNP)-driven point mutations on LL-37 structure and activity. Our results suggest that while the mutations had minimal impact on LL-37 activity, some mutations could reduce its antimicrobial activity and alter its structure.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Biotechnology & Applied Microbiology
Huihui Zhang, Xinyuan Zhang, Siyu Liang, Jing Wang, Yao Zhu, Wanjiang Zhang, Siguo Liu, Stefan Schwarz, Fang Xie
Summary: The combination of phage endolysin Ply2660 and antimicrobial peptide LL-37 showed superior bactericidal efficacy against drug-resistant biofilm-producing E. faecalis. The combination also suppressed biofilm formation and exhibited enhanced biofilm killing compared to individual treatments. In a murine peritoneal septicemia model, the Ply2660-LL-37 combination effectively suppressed E. faecalis dissemination and attenuated organ injury.
NPJ BIOFILMS AND MICROBIOMES
(2023)
Review
Immunology
Shalini Shah, Rachel A. F. Wozniak
Summary: Bacterial keratitis is a leading cause of vision loss globally. Immediate use of broad-spectrum antibiotics is crucial to adequately treat this aggressive disease, but antibiotic resistance is increasingly limiting the effectiveness of conventional therapies. This review discusses the pathogenesis of Staphylococcus aureus and Pseudomonas aeruginosa, two common causes of bacterial keratitis, and explores novel therapies under development.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Yun-Qi Song, Su Min Kyung, Suji Kim, Gun Kim, So Yeong Lee, Han Sang Yoo
Summary: Pseudomonas aeruginosa is a major pathogen in nosocomial infections, which are difficult to handle due to its biofilm-forming ability and carbapenem resistance. Antimicrobial peptides, such as RP557, have shown effectiveness in inhibiting biofilms. Our study assessed the effectiveness of RP557 on carbapenem-resistant P. aeruginosa planktonic cells and biofilms, providing a potential treatment option for carbapenem-resistant P. aeruginosa infection. This treatment could be helpful in managing severe nosocomial infections caused by carbapenem-resistant bacteria and improving patients' survival rates.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Sara Masihzadeh, Mansour Amin, Zahra Farshadzadeh
Summary: This study investigated the antibiofilm activity of the WLBU2 peptide against Pseudomonas aeruginosa isolates. Results showed that WLBU2 exhibited strong inhibitory and eradication potency against MDR and carbapenem-resistant strains of P. aeruginosa, both in vitro and in vivo.
Review
Cell Biology
Claudia C. C. Paredes-Amaya, Maria Teresa Ulloa, Victor Antonio Garcia-Angulo
Summary: The effects of antibiotics on bacteria and microbial communities are complex and not fully studied. Understanding the adaptive and physiological responses of bacteria to antimicrobials is crucial in the fight against antimicrobial resistance. Bacterial dependence on antibiotics, where antibiotics actually promote bacterial growth, is an important trait that needs further investigation to understand its implications in clinical aspects.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Oncology
Qian Xiao, Yanfen Luo, Wen Shi, Yang Lu, Rui Xiong, Xinggui Wu, Haihao Huang, Chanjing Zhao, Jianming Zeng, Cha Chen
Summary: The antimicrobial peptide LL-37 regulates the quorum sensing system in Pseudomonas aeruginosa, inhibiting the expression of virulence factors and potentially serving as a candidate for QS inhibition and treatment of Pseudomonas aeruginosa biofilms.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Article
Microbiology
Ronan A. Murphy, Matthew Coates, Sophia Thrane, Akshay Sabnis, James Harrison, Silke Schelenz, Andrew M. Edwards, Thomas Vorup-Jensen, Jane C. Davies
Summary: Pseudomonas aeruginosa is a common pathogen causing lung infections in people with cystic fibrosis. Glatiramer acetate, a drug used in multiple sclerosis treatment, has shown potential antipseudomonal activity. This study demonstrates that glatiramer acetate improves the efficacy of tobramycin, an antibiotic, against P. aeruginosa. It disrupts the bacterial cell wall and enhances the permeability of P. aeruginosa, allowing tobramycin to work more effectively. This research suggests that glatiramer acetate could be repurposed as an antibiotic resistance breaker for P. aeruginosa.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Malihe Mirzaee, Edita Holaskova, Alzbeta Micuchova, David J. Kopecny, Zhila Osmani, Ivo Frebort
Summary: This study demonstrates stable inheritance and expression of the LL-37 gene in barley over six generations, including two consecutive seasons of experimental field cultivation. The transgenic plants exhibited normal growth and remained fertile, with the produced LL-37 peptide retaining high antibacterial activity based on bacteria viability tests.
Article
Microbiology
Adam S. Bronson, Nina S. Baggett, Matthew T. Cabeen
Summary: Pyocins, interbacterial killing complexes produced by Pseudomonas aeruginosa, are primarily regulated by the activation of RecA due to DNA damage. However, our study reveals that the deletion of xerC enhances basal pyocin expression independently of RecA and that DNA damage-induced pyocin stimulation in Delta xerC cells is RecA-independent but dependent on PrtN. Moreover, inactivation of XerC recombinase activity leads to increased pyocin production, which is fully RecA dependent. These findings highlight the importance of XerC in regulating pyocin production and suggest potential strategies for targeting noncanonical pyocin production.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Roberto Vazquez, Antonio Domenech-Sanchez, Susana Ruiz, Julio Sempere, Jose Yuste, Sebastian Alberti, Pedro Garcia
Summary: Phage lysins are a potential alternative to antibiotics, especially for Gram-negative pathogens. In this study, a modified antimicrobial peptide derived from a phage lysin showed improved antibacterial activity, synergy with antibiotics, and low cytotoxicity.
Letter
Ophthalmology
Dalia G. Said, Andrew R. Ross, Marco Messina, Imran Mohammed, Harminder S. Dua
Letter
Ophthalmology
Imran Mohammed, Andrew Ross, John O. Britton, Dalia G. Said, Harminder S. Dua
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2019)
Article
Pathology
Delu Song, Yoshiyasu Ueda, Rupak Bhuyan, Imran Mohammed, Takashi Miwa, Damodar Gullipali, Hangsoo Kim, Lin Zhou, Ying Song, Hannah Schultz, Albert Bargoud, Joshua L. Dunaief, Wen-Chao Song
AMERICAN JOURNAL OF PATHOLOGY
(2019)
Review
Ophthalmology
Mouhamed A. Al-Aqaba, Virinder K. Dhillon, Imran Mohammed, Dalia G. Said, Harminder S. Dua
PROGRESS IN RETINAL AND EYE RESEARCH
(2019)
Article
Ophthalmology
Mouhamed Ali Al-Aqaba, Fady S. Anis, Imran Mohammed, Anjali Dias Samarawickrama Yapa, Winfried M. Amoaku, Harminder Singh Singh Dua
Summary: This study utilized in vivo confocal microscopy to describe the features of human limbal nerve corpuscles and their correlation with histological features. The study found a strong correlation between in vivo and histological results, indicating the potential use of IVCM in studying LNCs in normal and disease conditions.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Immunology
Darren Shu Jeng Ting, Roger W. Beuerman, Harminder S. Dua, Rajamani Lakshminarayanan, Imran Mohammed
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Ophthalmology
Imran Mohammed, Bina Kulkarni, Lana A. Faraj, Ali Abbas, Harminder S. Dua, Anthony J. King
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2020)
Article
Ophthalmology
Imran Mohammed, Debasmita Mohanty, Dalia G. Said, Manas Ranjan Barik, Mamatha M. Reddy, Ahmed Alsaadi, Sujata Das, Harminder Singh Dua, Ruchi Mittal
Summary: AMP expression is a consistent feature of FK, with HBD-1 and -2 being most consistently expressed while LL-37 is the least, indicating a certain specificity of AMP expression related to FK. These results will aid in identifying HBD sequence templates for designing FK-specific peptides for potential therapeutic use.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Ophthalmology
Rashmi Deshmukh, Darren Shu Jeng Ting, Ahmad Elsahn, Imran Mohammed, Dalia G. Said, Harminder Singh Dua
Summary: Ikervis is a useful topical treatment for managing ocular surface inflammatory diseases in real-world settings, but preparations with improved tolerability are needed to benefit a larger number of patients.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Multidisciplinary Sciences
Darren Shu Jeng Ting, Eunice Tze Leng Goh, Venkatesh Mayandi, Joanna M. F. Busoy, Thet Tun Aung, Mercy Halleluyah Periayah, Mario Nubile, Leonardo Mastropasqua, Dalia G. Said, Hla M. Htoon, Veluchamy Amutha Barathi, Roger W. Beuerman, Rajamani Lakshminarayanan, Imran Mohammed, Harminder S. Dua
Summary: The study successfully developed a novel antimicrobial therapy based on human-derived hybrid host defense peptides (HyHDPs) through combination of functional amino acids in parent peptides. The second-generation peptide CaD23 demonstrated good efficacy against various bacteria and minimal cytotoxicity to human cells. Pre-clinical murine studies showed that CaD23 was effective against Gram-positive bacteria without promoting antimicrobial resistance.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Darren Shu Jeng Ting, Jianguo Li, Chandra S. Verma, Eunice T. L. Goh, Mario Nubile, Leonardo Mastropasqua, Dalia G. Said, Roger W. Beuerman, Rajamani Lakshminarayanan, Imran Mohammed, Harminder S. Dua
Summary: CaD23 is a novel synthetic HDP with strong antimicrobial efficacy, especially in combination with antibiotics. Its rapid antimicrobial action is mainly attributed to its membrane-permeabilising mechanism, and MD simulations are useful for elucidating its mechanism of action and guiding design optimization.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Infectious Diseases
Waqas Ali, Ahmad Elsahn, Darren S. J. Ting, Harminder S. Dua, Imran Mohammed
Summary: One of the major challenges in the medical community today is the increasing antimicrobial resistance (AMR) coupled with the reduction in available antimicrobial treatments. The overuse of antibiotics has led to a significant rise in AMR, with estimates suggesting over 10 million lives could be lost by 2050. Host Defence Peptides (HDPs) have shown promise as an alternative to traditional antibiotics, demonstrating efficacy against currently resistant microbial variants. In light of the global COVID-19 pandemic, the potential use of HDPs as a therapeutic option and preventive measure against the spread of the SARS-CoV-2 variant has been examined.
Review
Medicine, General & Internal
Darren Shu Jeng Ting, Imran Mohammed, Rajamani Lakshminarayanan, Roger W. Beuerman, Harminder S. Dua
Summary: Vision is considered the most important sense in humans, and the ocular surface plays a crucial role in defending the eye against environmental stress and pathogens. Host defense peptides (HDPs) are innate immune molecules that have antimicrobial and other biological functions. This review provides an updated overview of HDPs at the ocular surface, their involvement in ocular diseases/conditions, current developments in HDP-based treatments for ocular diseases and infections, and the future potential of HDP-based clinical pharmacotherapy for ocular diseases.
FRONTIERS IN MEDICINE
(2022)
Meeting Abstract
Ophthalmology
Darren Ting, Dalia Said, Mario Nubile, Leonardo Mastropasqua, Veluchamy Barathi, Roger Beuerman, Rajamani Lakshminarayanan, Imran Mohammed, Harminder Dua
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)