2023-05-10·International journal of molecular sciences
Characterization and Engineering Studies of a New Endolysin from the Propionibacterium acnes Bacteriophage PAC1 for the Development of a Broad-Spectrum Artilysin with Altered Specificity.
作者: Christina Varotsou ; Georgios E Premetis ; Nikolaos E Labrou
The emergence of multidrug-resistant (MDR) bacteria has risen rapidly, leading to a great threat to global public health. A promising solution to this problem is the exploitation of phage endolysins. In the present study, a putative N-acetylmuramoyl-L-alanine type-2 amidase (NALAA-2, EC 22.214.171.124) from Propionibacterium bacteriophage PAC1 was characterized. The enzyme (PaAmi1) was cloned into a T7 expression vector and expressed in E. coli BL21 cells. Kinetics analysis using turbidity reduction assays allowed the determination of the optimal conditions for lytic activity against a range of Gram-positive and negative human pathogens. The peptidoglycan degradation activity of PaAmi1 was confirmed using isolated peptidoglycan from P. acnes. The antibacterial activity of PaAmi1 was investigated using live P. acnes cells growing on agar plates. Two engineered variants of PaAmi1 were designed by fusion to its N-terminus two short antimicrobial peptides (AMPs). One AMP was selected by searching the genomes of Propionibacterium bacteriophages using bioinformatics tools, whereas the other AMP sequence was selected from the antimicrobial peptide databases. Both engineered variants exhibited improved lytic activity towards P. acnes and the enterococci species Enterococcus faecalis and Enterococcus faecium. The results of the present study suggest that PaAmi1 is a new antimicrobial agent and provide proof of concept that bacteriophage genomes are a rich source of AMP sequences that can be further exploited for designing novel or improved endolysins.
2021-12-08·Microbiology spectrum2区 · 生物学
Design SMAP29-LysPA26 as a Highly Efficient Artilysin against Pseudomonas aeruginosa with Bactericidal and Antibiofilm Activity.
2区 · 生物学
作者: Tingting Wang ; Yongxiang Zheng ; Jiami Dai ; Junxiu Zhou ; Rong Yu ; Chun Zhang
Antimicrobial resistance (AMR) is a major issue to global health. The multidrug-resistant (MDR) Gram-negative infections, particularly infected by carbapenem-resistant pathogens, urgently need efficient antibiotics and novel therapy. However, the scientific challenges of aiming for innovative approaches against Gram-negative bacteria have hindered the research and development of antibiotic drugs. Phage-derived endolysins are bacteriolytic and specific for a bacterial species or genus, providing a promising antibiotic strategy. However, the outer membrane of Gram-negative bacteria could prevent the peptidoglycan layer from the hydrolysis of endolysins. Antimicrobial peptides usually destabilize the outer membrane and could enhance the antibiotic activity of endolysins. In this study, we designed new artilysins with antimicrobial-peptide SMAP29 fusion at the N-terminal of LysPA26 (named as AL-3AA, AL-9AA, and AL-15AA), and evaluated them. The results showed artilysin AL-3AA to be highly bactericidal; even 0.05 mg/mL AL-3AA could reduce 5.81 log units P. aeruginosa without EDTA in 60 min. It killed P. aeruginosa rapidly and dose-dependently through cell lysis. AL-3AA inhibited P. aeruginosa PAO1 biofilm formation and significantly decreased mature P. aeruginosa biofilms. It also had potential broad-spectrum activity against susceptible Gram-negative bacteria in the hospital, including K. pneumoniae and E. coli. The antibacterial mechanism investigation has provided valuable information about the antibacterial action of AL-3AA, which can lyse and disintegrate the bacterial quickly. These results suggested AL-3AA could be a new and promising antimicrobial agent for the combat of P. aeruginosa. IMPORTANCE Antimicrobial resistance (AMR) is a major issue to global health, particularly the multidrug-resistant (MDR) Gram-negative infections, which pose great challenges. Even new antibiotics research is ongoing, antibiotics used to treat Gram-negative bacteria in the clinical are limited in a small set of molecular scaffolds, and biomolecular categories of antibiotics are urgently needed. In this study, we designed new proteins by combining antimicrobial peptides and endolysins for synergistic bactericidal effects. One of designed proteins, named AL-3AA, showed highly bactericidal, and killed P. aeruginosa rapidly and dose-dependently through cell lysis. It also killed Klebsiella pneumoniae and Escherichia coli, showing potential broad-spectrum activity against susceptible Gram-negative bacteria in the hospital. All results suggest AL-3AA could be a new and promising antimicrobial agent for the combat of P. aeruginosa.
Acinetobacter baumannii Resistance: A Real Challenge for Clinicians.
3区 · 医学
作者: Rosalino Vázquez-López ; Sandra Georgina Solano-Gálvez ; Juan José Juárez Vignon-Whaley ; Jorge Andrés Abello Vaamonde ; Luis Andrés Padró Alonzo ; Andrés Rivera Reséndiz ; Mauricio Muleiro Álvarez ; Eunice Nabil Vega López ; Giorgio Franyuti-Kelly ; Diego Abelardo Álvarez-Hernández ; Valentina Moncaleano Guzmán ; Jorge Ernesto Juárez Bañuelos ; José Marcos Felix ; Juan Antonio González Barrios ; Tomás Barrientos Fortes
Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with A. baumannii have been documented. The most common risk factor for the acquisition of MDR A baumannii is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required.
TRIESENBERG, Liechtenstein--(BUSINESS WIRE)-- Lysando, leading biotech in antimicrobial proteins, proudly announces the addition of Mr. Jorge Cortell to its esteemed Advisory Board marking a significant milestone in the company's growth. As a serial entrepreneur and renowned visionary in healthcare technology he brings a wealth of expertise to Lysando's strategic direction.
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Jorge Cortell - Advisory Board Member Lysando AG
As Senior Advisor for Healthcare and Life Sciences at Harvard University Innovation Laboratories, and a technology advisor to NLC, Europe's largest HealthTech Venture Builder, Jorge Cortell's background positions him as a thought leader in the global industry. His profound understanding of both tech and business landscapes makes him an asset in guiding Lysando towards new heights of success.
“At Lysando, our mission is helping patients rather than simply selling treatments. Antibiotic resistance is estimated to claim over a million lives annually worldwide, posing an existential threat to society. Moreover, contamination of our environment by pharmaceuticals, particularly antibiotics, poses an alarming additional danger,” says Count Markus Matuschka de Greiffenclau, Chairman of the Board of Directors of Lysando AG. “With our Artilysin® technology, we are committed to combating resistance, promoting green pharma practices, and envisioning a future without fear of bacterial infections. As time is of the essence, we are delighted to have Jorge on board; a visionary who embodies innovation, comprehends AI, and supports Lysando's endeavour to save millions from pathogenic bacteria.”
“I am delighted to announce my appointment to the Advisory Board of this pioneer in the field of innovative antimicrobial solutions,” says Jorge Cortell, newly appointed Advisory Board member of Lysando AG. “Joining Lysando represents an exciting opportunity to contribute my expertise in cutting-edge technologies and their potential to revolutionize healthcare. I believe in Lysando's mission to address the global challenge of antimicrobial resistance and to improve patient outcomes through transformative therapeutic solutions. Together, we will strive to shape a healthier future by harnessing the power of science and innovation.”
Jorge Cortell's involvement on the Advisory Board promises to drive the company's mission, ultimately ushering in a future of improved quality of life for all.
About Lysando AG
Lysando is market leader for antimicrobial proteins, so‐called Artilysin® molecules. They can effectively eliminate problem‐causing bacteria without associated high risk of resistance formation and microbial disbalances. Artilysin® constitutes an innovative, proprietary, and environmentally friendly technology with a wide range of applications.
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Heading up AiCuris’ refocused pipeline will be Pritelivir, which is in phase 3 development to treat acyclovir-resistant herpes simplex virus infections.
AiCuris is doubling down on its infectious disease pipeline at the expense of its COVID-19 and foot infection programs.
“Sharpening its strategic focus” on a portfolio of therapies for infectious diseases in immunocompromised patients means the biotech will be able to accelerate development plans and prepare for market launch, the Wuppertal, Germany-based company said in a July 6 release.
The knock-on effect is that AiCuris “will discontinue research activities outside of this strategic scope.” While the company didn’t go into details of what activities will be scrapped, the COVID-19 therapy AIC649 was notable for its absence from today’s release.
The company received 5.9 million EUR ($6.4 million) in funding from a regional German government last year to advance the immune modulator as a potential way to slow progression of COVID-19. The therapy had been undergoing a clinical study in Germany and Africa.
Another program that wasn’t name-checked today was AiCuris’ collaboration with fellow German biotech Lysando. The two companies were working on Artilysin, a potential treatment for infected, chronic wounds such as diabetic foot infections.
“Unfortunately, anti-infective treatment options for this growing patient population are often limited and few companies are focusing on developing appropriate therapeutic candidates,” AiCuris CEO Larry Edwards said in the release. “This strategic change will allow us to be more efficient and effective from an operations perspective and ensure we are able to bring novel treatment options to patients in need.”
Heading up AiCuris’ refocused pipeline will be Pritelivir, which is in phase 3 development to treat acyclovir-resistant herpes simplex virus infections in immunocompromised patients. Topline data is due at the end of 2024.
Then there’s AIC468, an anti-sense RNA therapy due to enter the clinic early next year to prevent BK virus infection in kidney transplanted patients. The biotech is also working on preclinical programs designed to combat human adenovirus infections, with a key goal being to develop the first topical treatment specifically designed for ADV infections of the eye.
)--Amicogen, a leading biotech company specializing in industrial enzyme production and drug development, has partnered with Lysando, an innovative biotech company with expertise in the development of antimicrobial Artilysin
, to address the rising issue of mastitis in dairy cows caused by multi-resistant bacteria.
According to recent research, the overuse of antibiotics in animal husbandry has been driving a fast increase in multidrug-resistant pathogens. Approximately 70% of all antibiotics produced globally are used in agriculture, often as preventative measures, which has accelerated the spread of resistances.
Mastitis – a bacterial infection of the udder caused by various, often multi-resistant strains of bacteria – is rapidly spreading, particularly in Asia. This leads to animal suffering and significant wastage of milk production, causing the global dairy industry about $20-30 billion in annual revenue loss.
The partnership between Amicogen and Lysando aims to develop an innovative solution to this pressing issue. By leveraging their combined expertise, the companies set out to generate a treatment that is both effective and sustainable, reducing the economic impact of mastitis on farmers while improving animal welfare.
“We are excited to partner with Lysando to develop a novel and innovative solution against mastitis in dairy cows,” said Dr. Park, CEO of Amicogen. “This collaboration highlights the growing importance of joining forces in biotech and the potential for innovation to address critical challenges – also in agriculture.”
technology has shown great promise in addressing bacterial infections and we believe that this partnership will make a real difference in the fight against mastitis”, added Dr. Kerstin Emmrich, Director R&D, Lysando AG.
The joint effort between Amicogen and Lysando represents a significant step towards combatting the rising problem of antibiotic resistance and improving animal health. The companies envisage to continue their research to deliver innovative solutions for critical challenges.
Amicogen Inc (092040.KQ) is a CDMO and biotechnology company based in Jinju, South Korea. Amicogen is a leader in the development and production of specialty enzymes and proteins for the biopharmaceutical, food, cosmetics and other industries.
Lysando AG is market leader for antimicrobial proteins, so‐called Artilysin
molecules. They can effectively eliminate problem‐causing bacteria without associated high risk of resistance formation and microbial disbalances. Artilysin
constitutes an innovative, proprietary, and environmentally friendly technology with a wide range of applications.