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Antimicrobials: Discovery, clinical use, and development of resistance

Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.

List by Zhang-He Goh

Preprints:

Selection for antibiotic resistance is reduced when embedded in a natural microbial community

Uli Klümper, Mario Recker, Lihong Zhang, Xiaole Yin, Tong Zhang, Angus Buckling, William Gaze

https://www.biorxiv.org/content/10.1101/529651v1

The overuse of antibiotics in both medicine and agriculture, especially in the latter, has led to a drastic rise in antibiotic resistance over the last decade. Notably, the rise of antibiotic resistance has been so meteoric that it is now listed as one of the World Health Organisation (WHO) has listed as “one of the biggest threats to global health, food security, and development today”. In their preprint, Klumper et al. explored the ecological factors that affect the development of antimicrobial resistance in a microbial community.

Contribution of pretomanid to novel regimens containing bedaquiline with either linezolid or moxifloxacin and pyrazinamide in murine models of tuberculosis

Jian Xu, Si-Yang Li, Deepak V. Almeida, Rokeya Tasneen, Kala Barnes-Boyle, Paul J. Converse, Anna M. Upton, Khisimuzi Mdluli, Nader Fotouhi, Eric L. Nuermberger

https://www.biorxiv.org/content/10.1101/514661v1

As recently as 2018, the World Health Organisation described Multidrug-resistant TB (MDR-TB) as “a public health crisis and a health security threat”. This urgency necessitates the development of drug regimens to reduce resistance, as well as the discovery of drugs with new mechanisms of action. In their preprint, Xu et al. described tests of a combination of antitubercular drugs, including pretomanid, in three different murine models: nude mice, BALB/c mice, and C3HeB/FeJ mice.

Estimation of Pharmacokinetic Parameters of Continuous Intravenous Flucloxacillin infusion in the Outpatient Settings (PKFLUCLOX)

N Lwin, Z Liu, M Loewenthal, P Dobson, JW Yoo, P Galettis, K Lai, J Martin

https://www.biorxiv.org/content/10.1101/499848v1

Lwin et al. characterise the pharmacokinetics of intravenously-administered flucloxacillin and develop a model to aid in outpatient administration of flucloxacillin.

Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline

Ross D Overacker, Somdev Banerjee, George F Neuhaus, Selena Milicevic Sephton, Alexander Herrmann, James A Strother, Ruth Brack-Werner, Paul R Blakemore, Sandra Loesgen

https://www.biorxiv.org/content/10.1101/525105v1

Plant and marine sources of drugs have traditionally been favoured as a source for inspiration of drugs. Inspired by bioactive biaryl-containing natural products from these sources, Overacker et al. screen a library of these compounds for their their antiviral activity.

Targeting extracellular glycans: Tuning multimeric boronic acids for pathogen-selective killing of Mycobacterium tuberculosis

Collette S Guy, Matthew I Gibson, Elizabeth Fullam

https://www.biorxiv.org/content/10.1101/529743v1

Guy et al. report a class of multimeric boronic acids which kill Mycobacterium tuberculosis (Mtb)by binding specifically to the glycans on the Mtb cell envelope. In doing so, the authors demonstrate how future antitubercular drug discovery may involve new mechanisms of action which target unique extracellular components on Mtb.

Epidemiology of Staphylococcus aureus in Neonates on Admission to a Chinese Neonatal Intensive Care Unit

Wenjing Geng, Yujie Qi, Wenting Li, Thomas H McConvillle, Alexandra Hill Ricciuti, Emily Grohs, Lisa Saiman, Anne-Catrin Uhlemann

https://www.biorxiv.org/content/10.1101/529941v1

By identifying risk factors for nasal colonisation and transmission of Staphylococcus aureus in neonates admitted to a Chinese Neonatal Intensive Care Unit, Geng et al. contribute findings which support the need to actively monitor neonates for S. aureus to better control the spread of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA).

Amoxicillin inactivation by thiol-catalyzed cyclization reduces protein haptenation and antibacterial potency

María A. Pajares, Tahl Zimmerman, Francisco J. Sánchez-Gómez, Adriana Ariza, María J. Torres, Miguel Blanca, F. Javier Cañada, María I. Montañez, Dolores Pérez-Sala

https://www.biorxiv.org/content/10.1101/647966v1

In their preprint, Pajares et al. investigate the factors that determine amoxicillin bioavailability. The authors reinforce past research that amoxicillin bioavailability is indeed affected by redox status, and highlight the possibility that amoxicillin may interact with thiol-containing compounds.

Antimalarial drug mefloquine kills both trophozoite and cyst stages of Entamoeba Mefloquine and Entamoeba histolytica

Conall Sauvey, Gretchen Ehrenkaufer, Anjan Debnath, Ruben Abagyan

https://www.biorxiv.org/content/10.1101/501999v1

This preprint by Sauvey et al. reinforces the value in drug repurposing; specifically, it reminds us that even old drugs with considerable side effects can still be useful in the context of other infectious diseases.

Development and validation of serological markers for detecting recent exposure to Plasmodium vivax infection

Rhea J. Longley, Michael T. White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Leanne J. Robinson, Fumie Matsuura, Shih-Jung Zoe Liu, Connie S. N. Li-Wai-Suen, Wai-Hong Tham, Julie Healer, Christele Huon, Chetan E. Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L. Doolan, Xavier C. Ding, Iveth J. Gonzalez, James Kazura, Marcus Lacerda, Jetsumon Sattabongkot, Takafumi Tsuboi, Ivo Mueller

https://www.biorxiv.org/content/10.1101/481168v1

This preprint by Longley et al. underscores the role that big data plays in the world of infectious diseases. Indeed, amassing large amounts of data helps not just in drug discovery, but also in accelerating the development of diagnostic tests that are simultaneously more sensitive and specific, as well as more rapid and inexpensive.

Categories: bioinformatics , clinical trials , epidemiology , immunology , microbiology , pharmacology and toxicology , synthetic biology

 

Posted on: 21st May 2019 , updated on: 5th June 2019

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