#beta-lactamase

[nmsc-market-pulse]

Demystifying the Beta-lactam and Beta-lactamase Inhibitors Market: Trends and Insights

The Beta-lactam and Beta-lactamase Inhibitors Market represents a critical sector within the broader pharmaceutical industry, addressing the pressing global challenge of antimicrobial resistance (AMR).

According to the study by Next Move Strategy Consulting, the global Beta-lactam and Beta-lactamase Inhibitors Market size is predicted to reach USD 34.20 billion with a CAGR of 1.9% by 2030.

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Trends in the Beta-lactam and Beta-lactamase Inhibitors Market

Rising Prevalence of Antibiotic Resistance: Antibiotic resistance has emerged as a global public health crisis, with bacteria developing resistance to multiple classes of antibiotics. The overuse and misuse of antibiotics in human medicine, agriculture, and animal husbandry have accelerated the proliferation of resistant bacteria. In particular, the widespread dissemination of extended-spectrum beta-lactamases (ESBLs) and carbapenemases poses a significant threat to healthcare systems worldwide.

Technological Advancements in Drug Discovery: Advances in biotechnology, genomics, and computational biology are driving innovation in antimicrobial drug discovery. High-throughput screening techniques, structural biology, and virtual screening methods enable rapid identification and optimization of novel beta-lactamase inhibitors. Furthermore, the application of CRISPR-Cas9 technology facilitates the precise modification of bacterial genomes to study antimicrobial resistance mechanisms and develop novel therapeutic strategies.

Regulatory Initiatives and Antimicrobial Stewardship: Regulatory agencies are increasingly prioritizing antimicrobial stewardship and promoting the responsible use of antibiotics to mitigate the spread of resistant bacteria. In the United States, the Food and Drug Administration (FDA) has implemented guidelines for the development of antimicrobial drugs, emphasizing the importance of demonstrating clinical efficacy and safety in treating resistant infections. Similarly, the European Medicines Agency (EMA) has established regulatory frameworks to incentivize the development of new antibiotics through market exclusivity and streamlined approval processes.

Market Dynamics and Competitive Landscape: The Beta-lactam and Beta-lactamase Inhibitors Market is characterized by intense competition among pharmaceutical companies, biotechnology firms, and academic research institutions. Established players such as Pfizer, Merck & Co., and GlaxoSmithKline dominate the market with a diverse portfolio of beta-lactam antibiotics and inhibitors. However, emerging biotech startups and small to medium-sized enterprises (SMEs) are gaining traction by focusing on niche therapeutic areas, innovative drug delivery platforms, and strategic partnerships.

Collaborative Research and Development: Collaborative research consortia, public-private partnerships, and academic-industry collaborations are driving preclinical and clinical research in the field of antimicrobial drug discovery. Initiatives such as the Innovative Medicines Initiative (IMI) in Europe and the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) in the United States provide funding, expertise, and infrastructure to accelerate the development of novel antibiotics and beta-lactamase inhibitors.

Insights into Market Segmentation and Therapeutic Applications

The Beta-lactam and Beta-lactamase Inhibitors Market can be segmented based on product type, mechanism of action, route of administration, and therapeutic indication. Key product categories include beta-lactam antibiotics (e.g., penicillins, cephalosporins, carbapenems) and beta-lactamase inhibitors (e.g., clavulanic acid, sulbactam, tazobactam). Mechanistically, beta-lactamase inhibitors can be classified as competitive or suicide inhibitors, depending on their mode of enzyme inhibition. Furthermore, beta-lactam and beta-lactamase inhibitors can be administered via various routes, including oral, intravenous, and intramuscular routes, depending on the severity and site of infection.

Therapeutically, beta-lactam and beta-lactamase inhibitors are indicated for the treatment of a wide range of bacterial infections, including respiratory tract infections, urinary tract infections, skin and soft tissue infections, and intra-abdominal infections. Additionally, combination therapy with beta-lactam antibiotics and inhibitors has demonstrated efficacy against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae (CRE).

Future Perspectives and Challenges

Despite significant progress in antimicrobial drug discovery, the Beta-lactam and Beta-lactamase Inhibitors Market faces several challenges and uncertainties. These include:

Antibiotic Resistance: The continued evolution and dissemination of antibiotic-resistant bacteria pose a formidable challenge to the effectiveness of beta-lactam antibiotics and inhibitors. Strategies to combat resistance include the development of novel antibiotics with alternative mechanisms of action, combination therapy approaches, and the implementation of infection prevention and control measures.

Regulatory Hurdles: Regulatory agencies require robust clinical evidence to support the approval and marketing of new antibiotics and beta-lactamase inhibitors. Clinical trial design, patient recruitment, and endpoint selection present logistical and ethical challenges, particularly in the context of rare and multidrug-resistant infections.

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Economic Considerations: The economic viability of antibiotic development remains a concern for pharmaceutical companies, given the high costs and uncertain returns associated with antibiotic R&D. Market incentives, reimbursement policies, and public-private partnerships are essential to incentivize investment in antibiotic innovation and ensure access to effective antimicrobial therapies.

Global Health Equity: Access to essential antibiotics and beta-lactamase inhibitors remains uneven across different regions and socioeconomic groups. Disparities in healthcare infrastructure, affordability, and antibiotic stewardship practices contribute to the persistence of infectious diseases and antimicrobial resistance in low- and middle-income countries. Addressing these disparities requires a comprehensive approach involving governments, healthcare providers, and international organizations.

Research and Development Incentives: Encouraging investment in research and development (R&D) for new antibiotics and beta-lactamase inhibitors is crucial to address gaps in the current antimicrobial pipeline. Governments, philanthropic organizations, and private-sector stakeholders can provide financial incentives, grants, and tax credits to stimulate innovation in antimicrobial drug discovery. Additionally, initiatives such as priority review vouchers and market exclusivity extensions can incentivize pharmaceutical companies to prioritize antibiotic R&D and bring new treatments to market.

Antibiotic Stewardship Programs: Implementing comprehensive antibiotic stewardship programs is essential to promote rational antibiotic use, reduce unnecessary prescribing, and mitigate the emergence and spread of antibiotic-resistant bacteria. Healthcare facilities, including hospitals, clinics, and long-term care facilities, can establish multidisciplinary teams to develop and implement evidence-based guidelines for antibiotic prescribing, monitoring, and surveillance. Moreover, education and training initiatives for healthcare providers, patients, and the public are essential to raise awareness about the risks of antibiotic misuse and the importance of responsible antibiotic use.

Surveillance and Monitoring: Strengthening global surveillance systems and monitoring mechanisms is critical to track the epidemiology of antibiotic-resistant infections, detect emerging resistance trends, and inform public health interventions. National and international surveillance networks, such as the Centers for Disease Control and Prevention (CDC) in the United States and the European Centre for Disease Prevention and Control (ECDC) in Europe, play a vital role in collecting, analyzing, and disseminating data on antimicrobial resistance patterns. Collaborative efforts to harmonize surveillance methodologies, share data, and facilitate information exchange across borders are essential to enhance global preparedness and response to antibiotic-resistant threats.

Public Awareness and Education: Promoting public awareness and education about antimicrobial resistance is key to fostering behavioral change, empowering individuals to make informed decisions about antibiotic use, and reducing demand for unnecessary antibiotics. Public health campaigns, educational materials, and social media initiatives can raise awareness about the risks of antibiotic resistance, the importance of completing antibiotic courses as prescribed, and the role of individuals in preventing the spread of resistant bacteria. Furthermore, incorporating antimicrobial resistance education into school curricula and healthcare provider training programs can cultivate a culture of responsible antibiotic stewardship from an early age.

Conclusion

The Beta-lactam and Beta-lactamase Inhibitors Market plays a vital role in addressing the global threat of antimicrobial resistance and ensuring effective treatment options for bacterial infections. By understanding the key trends, insights, and challenges within this dynamic market, stakeholders can navigate regulatory, scientific, and economic complexities to drive innovation and improve patient outcomes. Collaboration across sectors, disciplines, and geographic regions is essential to develop sustainable solutions that preserve the efficacy of beta-lactam antibiotics and safeguard public health for future generations.

[nerdgirlnarrates]

Augmentin: a step up from those other pedestrian penicillins, augmentin contains both a beta-lactam and a beta-lactamase inhibitor as an added defense against pesky bacteria. It's one of the most commonly prescribed medications in the world, and it can be used to treat a wide variety of infections (in both humans and animals!) with good coverage against both gram positives and gram negatives. While it's pretty low-risk overall, it is one of the most frequent causes of idiosyncratic drug-induced hepatic injury (though the incidence comes out to about 43 in every 100,000 prescriptions of augmentin) (1).

Penicillin: the OG. The first antibiotic. Who could stand against her? Famously isolated from mold following Dr. Alexander Fleming's observations that it could keep bacteria at bay, penicillin was instrumental in ushering in the Age of Antibiotics. It saved lives throughout WWII and continues to save lives today with coverage against gram positives, gram negatives, and anaerobes--it even treats syphilis! Though its use has waned in the face of increased bacterial resistance, penicillin is still a strong contender in this tournament.

Vote for the best antibiotic

(1) deLemos AS, Ghabril M, Rockey DC, et al. Amoxicillin-Clavulanate-Induced Liver Injury. Dig Dis Sci. 2016;61(8):2406-2416. doi:10.1007/s10620-016-4121-6

[allthebrazilianpolitics]

Study detects increase of new generation of superbugs in Brazilian hospitals

The CDC-funded project shows detection rate has gone up nearly sixfold in seven years

A Brazilian study has demonstrated, for the first time, the increase of an enzyme linked to a new generation of multidrug-resistant bacteria in hospitals in the country, raising the alarm of hospital infection control commissions.

Named New Delhi metallo-beta-lactamase (NDM-1), the enzyme was first isolated in 2009 in India and has since caused outbreaks in that country, Pakistan, and England. Japan, Australia, Canada, and the United States have also recorded an increase in cases.

Continue reading.

[er-cryptid]

Methicillin

-- semi-synthetic penicillin

-- bulkier side chain than natural penicillin

-- harder for beta-lactamase to degrade

.

Patreon

[gasterofficial]

tell us abt science avemmmmmmmmm i love when ppl know things :]

oh man thats very wide criteria um. uhhhhhh right now i have scattered all over my bed all of my bio-organic chemistry notes i SHOULD BE STUDYING RIGHT NOW but anyway. lets see.

alrigghhttt so. biology is absolutely fascinating in the way everything fits together chemically and everything is repurposed in new ways that arose out of complete chance in early evolution. in so many different situations you can find examples of segments of chemical building blocks repurposed for different roles. common structural motifs such as phosphate groups or carbon rings or carboxylate (CO2-) groups are so ubiquitous in biochemistry and thats such an asset to your biology because it can pick apart sources of certain molecular groups and cut them up and rearrange them in just the way it needs to get certain products.

and the way it does that is so astoundingly complex and that's through metabolic pathways which are made possible by enzymes. so the thing about enzymes is that they are complex large molecules that are able to hold smaller molecules in really specific orientations so that chemical reactions can proceed both WAY faster (catalysis) and with way greater specificity, meaning that they can prevent unwanted byproducts by being produced instead of one specific target molecule. this is in comparison to pure laboratory synthesis to build a molecule, which is way slower by virtue of not having evolved the most efficient way to do a reaction– it's just chemists doing reactions in a certain order to make sure they receive the product they want based on how those reactions will take place. but enzymes force molecules into specific orientations so that getting the wrong outcome isn't even a consideration.

there's pockets of certain molecular groups in very specific orientations within enzymes that act as latching on points for the molecule the enzyme is targeting. and then there are other groups that are built in such a way that they can proceed with a specific chemical reaction in a precisely targeted location. it forces a reaction to happen in that specific location, and also to happen immediately when it might otherwise be determined by how likely a molecule is to bump into another in a very specific way. which is often.... extremely unlikely. there's chemical reactions that would take MILLIONS OF YEARS without their specific enzyme to catalyze them. we have even identified enzymes that are so efficient that they literally could not cause their respective chemical reactions to proceed any faster without messing with the literal physics of our universe.

in fact! one such "perfect enzyme" is beta-lactamase, which is an enzyme that bacteria evolved to break apart OTHER enzymes found in antibiotics that disrupt the formation of bacterial cell walls. you might be familiar with it– it's the source of one type of antibiotic resistance in bacteria, and it's the reason MRSA is so dangerous. thankfully, there are enzymes that have been evolved to combat the enzymes that the BACTERIA evolved, and these are what are used in treatments for antibiotic-resistant bacteria. it's a literal evolutionary, biological arms race.

so you can see how it's really quite incredible that evolution was able to produce something that is SO GOOD at its job, and that really accounts for much of the reason life exists as we know it. and it's all because in the beginning of things, way back before even single celled organisms existed, atoms were colliding to form molecules that collided with each other in happenstance ways, until chains of molecules were built up that just so happened to collide until they formed more complex chains that interacted with each other in more complex ways... in fact, that early molecular evolutioni s the focus of my bio-organic professor's research! which i hope to maybe work on this upcoming summer.

but anyway. half-coherent biochemistry infodump for you. idk if i repeated things a lot or whatever im not reading it again enjoy <3

[mcatmemoranda]

Centor criteria (determines the need for strep testing and culture): 1 point for fever, tonsillar exudates, tender anterior cervical lymph nodes, absence of cough, and age <15. Subtract 1 point if age >44. Score of -1 to 1: no antibiotic, no throat culture. Score of 2 or 3: throat culture, treat with antibiotic if throat culture is positive. Score of 4 or 5: treat empirically with antibiotic. Complications of strep throat include acute rheumatic fever, and post-streptococcal glomerulonephritis. Tx of strep throat will prevent acute rheumatic fever, but will not prevent post-streptococcal glomerulonephritis.

From UpToDate:

Importance of treatment – Group A Streptococcus (GAS), or Streptococcus pyogenes, is the leading bacterial cause of tonsillopharyngitis in adults and children worldwide. GAS is one of the few causes of tonsillopharyngitis or pharyngitis for which antibiotic treatment is recommended.

The goals of antibiotic therapy for GAS pharyngitis include symptom relief, preventing complications, and preventing transmission to others.

●Whom to treat – We recommend antibiotic treatment for any patient with symptomatic pharyngitis or tonsillopharyngitis who has a positive rapid antigen test or culture for GAS (Grade 1A). We generally do not treat patients who do not have microbiologic confirmation of infection or who are chronic carriers.

●Treatment recommendations

•Preferred treatment for adults – For most adults, we treat with oral penicillin V 500 mg two to three times daily for a total of 10 days. Penicillin is the treatment of choice for GAS pharyngitis due to its efficacy, safety, narrow spectrum, and low cost.

•Preferred treatment for children – For most children, we use either oral penicillin V or amoxicillin. Amoxicillin is often preferred for young children because the taste of the amoxicillin suspension is more palatable than that of penicillin.

•Treatment for patients with a history of acute rheumatic fever – For patients with a history of acute rheumatic fever or for those who may not adhere to oral therapy, we select among oral penicillin, oral amoxicillin, or a single dose of intramuscular penicillin based on drug availability, cost, and patient values and preferences.

•Alternatives for patients who cannot tolerate penicillin – Cephalosporins, clindamycin, and macrolides are alternatives for patients who are allergic to penicillin or who cannot otherwise tolerate penicillin. Selection among these agents is based on the nature of the drug allergy or intolerance and local antibiotic resistance rates.

●Symptom resolution and return to work – Fever and sore throat typically resolve within one to three days. Most patients can return to work, school, or daycare after 12 to 24 hours of antibiotic therapy, provided they are afebrile and otherwise well.

A test of cure is usually not needed for patients who are asymptomatic at the end of a course of antibiotic therapy, except for those with a history of acute rheumatic fever or in other special circumstances.

●Management of persistent symptoms after a course of antibiotics – For patients who have persistent or recurrent symptoms after completing a course of antibiotic therapy, we repeat microbiologic testing when symptoms are compatible with GAS infection. Because chronic GAS carriage can occur after antibiotic therapy, we generally avoid testing in patients who have symptoms that are more compatible with viral pharyngitis or other etiology.

For patients with microbiologically proven recurrent or persistent GAS pharyngitis, we repeat a 10-day course of antibiotic therapy (Grade 2C) and generally select an antibiotic that has greater beta-lactamase stability than the one used initially. Tonsillectomy is rarely indicated for such patients.

●Prophylaxis for patients with a history of acute rheumatic fever – Antibiotic prophylaxis is used for patients with a history of acute rheumatic fever because these patients are at high risk for recurrence and for the development of chronic valvular heart disease. Antibiotic prophylaxis is not recommended for chronic carriers, except in special circumstances.

[blueiight]

tagged by @firegiftlouis appreciate u💕

Last Song I listened to: a cry, a smile, a dance by judith sephuma

Last Movie: i aint watch a movie since i went to see wakanda forever but i unironically wanna see the cocaine bear & creed III. forgive my taste

Currently Reading: antimicrobial resistance patterns in extended-spectrum beta lactamase in [REDACTED AREA] & maladies of empire by jim downs.... contemplating a tvc reread but know ill have negative time in my day to do such

Tagging: anyone can do so...

[teachingrounds]

CRE = Carbapenem-Resistant Enterobacteriaceae. Carbapenems are a newer class of beta-lactamase antibiotics; CRE bacteria may also be resistant to unrelated drugs such as fluoroquinolones. Enterobacteriaceae is the name of a family of Gram-negative bacteria (E. coli, Klebsiella, Salmonella, etc.), many of which live in the human gut. Some patients came down with CRE after being scoped with the same endoscope as another patient with CRE in their stomach, intestines, or lungs. This category includes bacteria that have certain resistance factors such as KPC , NDM-1, and VIM. Treat with old and/or toxic drugs such as polymyxins, fosfomycin, and (sometimes) aminoglycosides (susceptibility varies).

• KPC = Klebsiella pneumoniae carbapenemase. A resistance factor that helps bacteria survive carbapenems and other beta-lactamase antibiotics. There was an outbreak in an NIH hospital.

• NDM-1 = New Delhi Metallobeta-lactamase 1. First identified in India and now in 140 countries, this plasmid moves promiscuously among different species of bacteria. Bad news for wound infections, pneumonias, meningitis, and blood infections.

• VIM = Verona Integron-Mediated Metallo-betalactamase. Like NDM-1, makes bugs resistant to beta-lactamase antibiotics such as penicillin or ceftriaxone.

[healthcare-skyquest]

Antibiotics Market: Combating Bacterial Infections in a New Era of Medicine

The Antibiotics market plays a crucial role in global healthcare by providing treatments that combat bacterial infections. As antibiotic resistance rises, the market is witnessing both challenges and innovations, making it essential for healthcare providers and decision-makers to stay informed. This article explores the latest trends, market segmentation, key growth drivers, and leading companies in the antibiotics industry.

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Market Overview

According to SkyQuest’s Antibiotics Market report, the global antibiotics market is valued at USD 41.4 billion in 2023 and is projected to grow at a CAGR of 2.5% during the forecast period. This growth is propelled by the increasing incidence of infectious diseases, the rising global population, and advancements in antibiotic development.

Market Segmentation

By Product Type:

Beta-Lactam and Beta-Lactamase Inhibitors: Widely used for treating a variety of bacterial infections, including respiratory and urinary tract infections.

Quinolones: Effective against a broad spectrum of bacterial pathogens, commonly used for respiratory infections.

Macrolides: Used primarily for respiratory infections and soft tissue infections.

Aminoglycosides: Target severe bacterial infections, especially in hospital settings.

Tetracyclines: Commonly used for skin infections, respiratory infections, and sexually transmitted diseases.

Others: Includes specialized antibiotics for niche infections or resistant bacterial strains.

By Spectrum of Activity:

Broad-Spectrum Antibiotics: Effective against a wide variety of bacteria, frequently prescribed for undiagnosed infections.

Narrow-Spectrum Antibiotics: Target specific bacteria, reducing the risk of resistance and minimizing side effects.

By Route of Administration:

Oral Antibiotics: Convenient for outpatient care and commonly prescribed for less severe infections.

Injectable Antibiotics: Typically used in hospitals for serious infections or when rapid treatment is needed.

Topical Antibiotics: Applied directly to the skin to treat local infections or prevent wound infections.

By End-User:

Hospitals & Clinics: Major users of antibiotics, especially for severe infections requiring immediate attention.

Pharmacies: Provide antibiotics for outpatient care, over-the-counter purchases, or prescription-based sales.

Research Laboratories: Focus on the development of new antibiotics and testing their efficacy against resistant bacteria.

Get more info at: — https://www.skyquestt.com/report/antibiotics-market

Key Growth Drivers

Rising Prevalence of Infectious Diseases: The continuous rise in bacterial infections worldwide, especially in developing regions, drives the demand for antibiotics.

Antibiotic Resistance: The emergence of drug-resistant bacteria necessitates the development of new antibiotics, boosting market growth.

Government Support and Initiatives: Various global health organizations and governments are actively funding research to combat antibiotic resistance.

Technological Advancements: Progress in biotechnology and genetic research is aiding the development of novel antibiotics.

Leading Companies in the Market

SkyQuest’s report highlights several key players in the Antibiotics market, including:

Merck & Co., Inc., Allergan plc (AbbVie), GlaxoSmithKline plc., Pfizer Inc., Novartis AG, Sanofi S.A., AstraZeneca plc, Johnson & Johnson, Teva Pharmaceutical Industries Ltd., Mylan N.V., Eli Lilly and Company, Bayer AG, Bristol-Myers Squibb Company, AbbVie Inc., Astellas Pharma Inc., Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Roche Holding AG, Sun Pharmaceutical Industries Ltd., Takeda Pharmaceutical Company Limited.

Challenges and Opportunities

The antibiotics market faces significant challenges, including antibiotic resistance and stringent regulatory approval processes. However, these challenges also create opportunities for innovation in developing next-generation antibiotics and alternative therapies.

Future Outlook

The future of the antibiotics market is shaped by ongoing efforts to combat antibiotic resistance and the development of advanced, targeted therapies. As companies invest in research and innovation, the market is expected to see steady growth. For more detailed insights and strategic recommendations, refer to SkyQuest’s in-depth Antibiotics Market report.

The Antibiotics market remains a cornerstone of global healthcare, with ongoing advancements aimed at tackling bacterial infections and resistance. Decision-makers who focus on innovation and the development of new antibiotics will stay at the forefront of this critical healthcare sector. For more in-depth insights and emerging trends, consult SkyQuest's Antibiotics Market report.

[aingopharma]

Introduction of Faropenem and Potassium Clavulanate Tablets

Bacterial infections can range from mild to severe, often requiring a tailored antibiotic regimen for effective treatment. Faropenem and Potassium Clavulanate Tablets combine two powerful agents to combat a broad spectrum of bacterial pathogens. This combination therapy is particularly useful against infections caused by beta-lactamase-producing bacteria, which can resist many common antibiotics. In this article, we’ll explore the uses, dosage, benefits, and potential side effects of Faropenem and Potassium Clavulanate Tablets. Understanding how this medication works can help you make informed decisions about your healthcare.

What are Faropenem and Potassium Clavulanate Tablets?

Faropenem and Potassium Clavulanate are combined in a single formulation to enhance the antibacterial efficacy of Faropenem.

Faropenem: A beta-lactam antibiotic belonging to the penem class, Faropenem is effective against a wide range of gram-positive and gram-negative bacteria. It works by inhibiting the synthesis of the bacterial cell wall, leading to bacterial cell death.

Potassium Clavulanate: A beta-lactamase inhibitor, Potassium Clavulanate extends the spectrum of Faropenem by inhibiting the beta-lactamase enzymes produced by bacteria. These enzymes can break down beta-lactam antibiotics, rendering them ineffective.

Together, this combination offers a robust defense against resistant bacterial strains, making it a valuable option for treating complex infections.

[nerdgirlnarrates]

Flucloxacillin: another pencillin, this time the most commonly prescribed narrow-spectrum penicillinase-resistant penicillin in the UK. Apparently, it was not marketed much in the US and Canada, where dicloxacillin filled its role. Flucloxacillin is used almost exclusively for gram positive infections, especially Staph aureus, though it can be also be used for pre-op prophylaxis.

Zosyn (pip/tazo): One of the big guns. Like augmentin, this combo therapy includes both a penicillin and a beta-lactamase inhibitor; unlike augmentin, it covers pseudomonas. Zosyn is crucial for treating nosocomial infections and often one of the first drugs we reach for when empirically broadening antibiotics. It is also first line for neutropenic fever.

Vote for the best antibiotic

[swissforextrading]

A new AI approach to protein design

07.08.24 - EPFL researchers a novel AI-driven model designed to predict protein sequences from backbone scaffolds, incorporating complex molecular environments. It promises significant advancements in protein engineering and applications across various fields, including medicine and biotechnology. Image caption: Schematic representation of sequence prediction with CARBonAra. The geometric transformer samples the sequence space of the beta-lactamase TEM-1 enzyme (in grey) complexed a natural substrate (in cyan) to produce new well folded and active enzymes. Credit: Alexandra Banbanaste (EPFL) Designing proteins that can perform specific functions involves understanding and manipulating their sequences and structures. This task is crucial for developing targeted treatments for diseases and creating enzymes for industrial applications. One of the grand challenges in protein engineering is designing proteins de novo, meaning from scratch, to tailor their properties for specific tasks. This has profound implications for biology, medicine, and materials science. For instance, engineered proteins can target diseases with high precision, offering a competitive alternative to traditional small molecule-based drugs. Additionally, custom-designed enzymes, which act as natural catalysts, can facilitate rare or nonexistent reactions in nature. This capability is particularly valuable in the pharmaceutical industry for synthesizing complex drug molecules and in environmental technology for breaking down pollutants or plastics more efficiently. A team of scientists led by Matteo Dal Peraro at EPFL has now developed CARBonAra (Context-aware Amino acid Recovery from Backbone Atoms and heteroatoms), an AI-driven model that can predict protein sequences, but by taking into account the restraints imposed by different molecular environments – a unique accomplishment. CARBonAra is trained on a dataset of approximately 370,000 subunits, with an additional 100,000 for validation and 70,000 for testing from the Protein Data Bank (PDB). CARBonAra builds on the architecture of the Protein Structure Transformer (PeSTo) framework – also developed by Lucien Krapp in Dal Peraro’s group. It uses geometric transformers, which are deep learning models that process spatial relationships between points, such as atomic coordinates, to learn and predict complex structures. CARBonAra can predict amino acid sequences from backbone scaffolds, the structural frameworks of protein molecules. However, one of CARBonAra’s standout features is its context awareness, which is especially demonstrated in how it improves sequence recovery rates – the percentage of correct amino acids predicted at each position in a protein sequence compared to a known reference sequence. CARBonAra significantly improved recovery rates when it includes molecular “contexts”, such as protein interfaces with other proteins, nucleic acids, lipid or ions. “This is because the model is trained with all sort of molecules and relies only on atomic coordinates, thus that it can handle not only proteins,” explains Dal Peraro. This feature in turn enhances the model's predictive power and applicability in real-life, complex biological systems. The model does not perform well only in synthetic benchmarks but was experimentally validated. The researchers used CARBonAra to design new variants of the TEM-1 β-lactamase enzyme, which is involved in the development of antimicrobial resistance. Some of the predicted sequences, differing by approximatively 50% from the wild-type sequence, were folded correctly and preserve some catalytical activity at high temperatures, when the wild-type enzyme is already inactive. The flexibility and accuracy of CARBonAra open new avenues for protein engineering. Its ability to take into account complex molecular environments makes it a valuable tool for designing proteins with specific functions, enhancing future drug discovery campaigns. In addition,… http://actu.epfl.ch/news/a-new-ai-approach-to-protein-design (Source of the original content)

[moleculardepot]

Recombinant Beta Lactamase

Recombinant Beta Lactamase Catalog number: B2017297 Lot number: Batch Dependent Expiration Date: Batch dependent Amount: 10 mg Molecular Weight or Concentration: 28.9 kDa Supplied as: Powder Applications: a molecular tool for various biochemical applications Storage: −20°C Keywords: β-Lactamase, EC 3.5.2.6, TEM-1 Grade: Biotechnology grade. All products are highly pure. All solutions are made…

[mcatmemoranda]

I saw an 11-day old baby with paronychia.

Paronychia — Acute paronychia is a painful bacterial infection of the periungual tissues caused by S. aureus and group A Streptococcus [77]. The inciting event is a mechanical lesion of the periungual skin, usually caused by trauma. Paronychia is also a frequent adverse event in children treated with BRAF and MEK inhibitor anticancer agents [78]:

●Clinical features and diagnosis – Acute paronychia presents with pain, swelling, and erythema of the nail folds. Formation of pus along the paronychial fold can occasionally result in the formation of an abscess involving the hyponychium and the area below the nail plate (picture 21). Due to the fragility of the nail matrix in children, even a mild, acute paronychia may induce a permanent nail dystrophy. The diagnosis of paronychia is made clinically.

●Treatment and prognosis – Systemic antibiotics are the first-line therapy for acute paronychia without abscess in children. Empirical treatment is started with beta-lactamase-resistant antibiotics (eg, flucloxacillin, dicloxacillin, cloxacillin). Drainage is indicated if there is abscess.

Treatment — The treatment of acute paronychia includes local skin-care measures, topical or oral antibiotics, and surgical modalities, depending upon the severity of inflammation and presence or absence of abscess or associated ingrown toenail. There are no high-quality studies evaluating the use of oral versus topical antibiotics for uncomplicated paronychia or the use of oral antibiotics in addition to surgical incision and drainage for acute paronychia with abscess [28]. The approach to treatment is thus based upon clinical experience and limited evidence from observational studies (algorithm 1).

Paronychia without abscess — In patients with inflammation without abscess formation, treatment with topical antibiotics and warm water or antiseptic soaks (eg, chlorhexidine, povidone-iodine) multiple times per day is usually effective (algorithm 1) [29]. We typically instruct the patient to apply an antistaphylococcal antibiotic (eg, triple antibiotic ointment or mupirocin) after each warm soak. Warm soaks should last 10 to 15 minutes.