{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:41:11Z","timestamp":1768509671415,"version":"3.49.0"},"posted":{"date-parts":[[2024,4,9]]},"group-title":"Microbiology","reference-count":98,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. We previously found that growth productivity, which captures the relationship between [ATP] and growth, can account for the strength of the inoculum effect for bactericidal antibiotics. However, the molecular pathway(s) underlying this relationship, and therefore determining the inoculum effect, remain undiscovered. We show that nucleotide synthesis can determine the relationship between [ATP] and growth, and thus the strength of inoculum effect in an antibiotic class-dependent manner. Specifically, and separate from activity through the tricarboxylic acid cycle, we find that transcriptional activity of genes involved in purine and pyrimidine synthesis can predict the strength of the inoculum effect for \u03b2-lactam and aminoglycosides antibiotics, respectively. Our work highlights the antibiotic class-specific effect of purine and pyrimidine synthesis on the severity of the inoculum effect and paves the way for intervention strategies to reduce the inoculum effect in the clinic.<\/jats:p>","DOI":"10.1101\/2024.04.09.588696","type":"posted-content","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:40:16Z","timestamp":1712709616000},"source":"Crossref","is-referenced-by-count":0,"title":["Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and \u03b2-lactam antibiotics"],"prefix":"10.64898","author":[{"given":"Daniella M.","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Marzouk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline","family":"Cole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marla C.","family":"Fortoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saipranavi Reddy","family":"Kethireddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehan","family":"Contractor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habibul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trent","family":"Moulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariane R.","family":"Kalifa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estefania Marin","family":"Meneses","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximiliano Barbosa","family":"Mendoza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Masud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheena","family":"Pubien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Milanes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Diaz-Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison J.","family":"Lopatkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024041108001094000_2024.04.09.588696v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00649-x"},{"key":"2024041108001094000_2024.04.09.588696v1.2","doi-asserted-by":"crossref","unstructured":"M. S. Butler , I. R. Henderson , R. J. Capon , M. A. Blaskovich , Antibiotics in the clinical pipeline as of December 2022. The Journal of Antibiotics, 1\u201343 (2023).","DOI":"10.1038\/s41429-023-00671-6"},{"key":"2024041108001094000_2024.04.09.588696v1.3","unstructured":"J. O\u2019Neill , Tackling drug-resistant infections globally: final report and recommendations. (2016)."},{"key":"2024041108001094000_2024.04.09.588696v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3380"},{"key":"2024041108001094000_2024.04.09.588696v1.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2000631"},{"key":"2024041108001094000_2024.04.09.588696v1.6","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/s41396-018-0090-4","article-title":"Cooperation, competition and antibiotic resistance in bacterial colonies","volume":"12","year":"2018","journal-title":"The ISME journal"},{"key":"2024041108001094000_2024.04.09.588696v1.7","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41396-023-01393-1","article-title":"Cooperative antibiotic resistance facilitates horizontal gene transfer","volume":"17","year":"2023","journal-title":"The ISME Journal"},{"key":"2024041108001094000_2024.04.09.588696v1.8","doi-asserted-by":"crossref","unstructured":"L. Dieltjens et al., Inhibiting bacterial cooperation is an evolutionarily robust anti-biofilm strategy. Nature Communications 11, 107 (2020).","DOI":"10.1038\/s41467-019-13660-x"},{"key":"2024041108001094000_2024.04.09.588696v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910934107"},{"key":"2024041108001094000_2024.04.09.588696v1.10","doi-asserted-by":"crossref","unstructured":"Y. Tanouchi , A. Pai , N. E. Buchler , L. You , Programming stress-induced altruistic death in engineered bacteria. Molecular systems biology 8, 626 (2012).","DOI":"10.1038\/msb.2012.57"},{"key":"2024041108001094000_2024.04.09.588696v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.3.361"},{"key":"2024041108001094000_2024.04.09.588696v1.12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.90.6.595"},{"key":"2024041108001094000_2024.04.09.588696v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/25.4.621"},{"key":"2024041108001094000_2024.04.09.588696v1.14","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.9.3.440"},{"key":"2024041108001094000_2024.04.09.588696v1.15","doi-asserted-by":"crossref","unstructured":"C. Tan et al., The inoculum effect and band-pass bacterial response to periodic antibiotic treatment. Molecular Systems Biology 8, 617 (2012).","DOI":"10.1038\/msb.2012.49"},{"key":"2024041108001094000_2024.04.09.588696v1.16","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.1.223"},{"key":"2024041108001094000_2024.04.09.588696v1.17","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.24.4.568"},{"key":"2024041108001094000_2024.04.09.588696v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.11.012"},{"key":"2024041108001094000_2024.04.09.588696v1.19","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.2034"},{"key":"2024041108001094000_2024.04.09.588696v1.20","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01410-07"},{"key":"2024041108001094000_2024.04.09.588696v1.21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02190-12"},{"key":"2024041108001094000_2024.04.09.588696v1.22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0002-9343(87)90625-5","article-title":"Effect of inoculum size on in vitro activity of norfloxacin against fecal anaerobic bacteria: rationale for selective decontamination of the digestive tract","volume":"82","year":"1987","journal-title":"The American journal of medicine"},{"key":"2024041108001094000_2024.04.09.588696v1.23","doi-asserted-by":"crossref","first-page":"2049936119886504","DOI":"10.1177\/2049936119886504","article-title":"Adjunctive ceftaroline in combination with daptomycin or vancomycin for complicated methicillin-resistant Staphylococcus aureus bacteremia after monotherapy failure","volume":"6","year":"2019","journal-title":"Therapeutic advances in infectious disease"},{"key":"2024041108001094000_2024.04.09.588696v1.24","doi-asserted-by":"crossref","first-page":"912","DOI":"10.3390\/antibiotics9120912","article-title":"In Vitro Activities and Inoculum Effects of Ceftazidime-Avibactam and Aztreonam-Avibactam against Carbapenem-Resistant Enterobacterales Isolates from South Korea","volume":"9","year":"2020","journal-title":"Antibiotics"},{"key":"2024041108001094000_2024.04.09.588696v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/128.Supplement_2.S386"},{"key":"2024041108001094000_2024.04.09.588696v1.26","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00317-09"},{"key":"2024041108001094000_2024.04.09.588696v1.27","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03270330059022"},{"key":"2024041108001094000_2024.04.09.588696v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(78)90790-8"},{"key":"2024041108001094000_2024.04.09.588696v1.29","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-003-0959-6"},{"key":"2024041108001094000_2024.04.09.588696v1.30","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1089\/mdr.2014.0059","article-title":"The effect of inoculum size on selection of in vitro resistance to vancomycin, daptomycin, and linezolid in methicillin-resistant Staphylococcus aureus","volume":"20","year":"2014","journal-title":"Microbial Drug Resistance"},{"key":"2024041108001094000_2024.04.09.588696v1.31","doi-asserted-by":"publisher","DOI":"10.1086\/342698"},{"key":"2024041108001094000_2024.04.09.588696v1.32","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1771-1777.2000"},{"key":"2024041108001094000_2024.04.09.588696v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.08.021"},{"key":"2024041108001094000_2024.04.09.588696v1.34","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1111\/1462-2920.14796","article-title":"The public and private benefit of an impure public good determines the sensitivity of bacteria to population collapse in a snowdrift game","volume":"21","year":"2019","journal-title":"Environmental microbiology"},{"key":"2024041108001094000_2024.04.09.588696v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn554"},{"key":"2024041108001094000_2024.04.09.588696v1.36","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.66.4.1706-1710.2000"},{"key":"2024041108001094000_2024.04.09.588696v1.37","doi-asserted-by":"crossref","first-page":"eadd0924","DOI":"10.1126\/sciadv.add0924","article-title":"Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics","volume":"8","year":"2022","journal-title":"Science Advances"},{"key":"2024041108001094000_2024.04.09.588696v1.38","doi-asserted-by":"crossref","unstructured":"A. J. Lopatkin et al., Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate. Nature microbiology, 1\u20139 (2019).","DOI":"10.1038\/s41564-019-0536-0"},{"key":"2024041108001094000_2024.04.09.588696v1.39","doi-asserted-by":"crossref","first-page":"e74062","DOI":"10.7554\/eLife.74062","article-title":"Fast bacterial growth reduces antibiotic accumulation and efficacy","volume":"11","year":"2022","journal-title":"Elife"},{"key":"2024041108001094000_2024.04.09.588696v1.40","first-page":"e00013","article-title":"Role of the SOS response in the generation of antibiotic resistance in vivo","volume":"65","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2024041108001094000_2024.04.09.588696v1.41","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1021\/acsinfecdis.9b00204","article-title":"(p) ppGpp and the stringent response: an emerging threat to antibiotic therapy","volume":"5","year":"2019","journal-title":"ACS infectious diseases"},{"key":"2024041108001094000_2024.04.09.588696v1.42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.chembiol.2016.12.015","article-title":"Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control","volume":"24","year":"2017","journal-title":"Cell chemical biology"},{"key":"2024041108001094000_2024.04.09.588696v1.43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509743112"},{"key":"2024041108001094000_2024.04.09.588696v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"2024041108001094000_2024.04.09.588696v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.016"},{"key":"2024041108001094000_2024.04.09.588696v1.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba0862"},{"key":"2024041108001094000_2024.04.09.588696v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/nature10069"},{"key":"2024041108001094000_2024.04.09.588696v1.48","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10803"},{"key":"2024041108001094000_2024.04.09.588696v1.49","doi-asserted-by":"crossref","unstructured":"B. Hove-Jensen et al., Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance. Microbiol Mol Biol Rev 81, (2017).","DOI":"10.1128\/MMBR.00040-16"},{"key":"2024041108001094000_2024.04.09.588696v1.50","unstructured":"D. L. Nelsen , M. M. Cox , Lehninger principles of biochemistry. (Macmillan Learning, 2021)."},{"key":"2024041108001094000_2024.04.09.588696v1.51","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.1123.1126.1122"},{"key":"2024041108001094000_2024.04.09.588696v1.52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040037"},{"key":"2024041108001094000_2024.04.09.588696v1.53","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1016\/S0021-9258(18)50771-7","article-title":"Glutamine phosphoribosylpyrophosphate amidotransferase from Escherichia coli. Purification and properties","volume":"254","year":"1979","journal-title":"Journal of Biological Chemistry"},{"key":"2024041108001094000_2024.04.09.588696v1.54","doi-asserted-by":"publisher","DOI":"10.1021\/bi00015a018"},{"key":"2024041108001094000_2024.04.09.588696v1.55","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1002\/j.1460-2075.1984.tb02046.x","article-title":"Structure of the Escherichia coli pyrE operon and control of pyrE expression by a UTP modulated intercistronic attentuation","volume":"3","year":"1984","journal-title":"The EMBO Journal"},{"key":"2024041108001094000_2024.04.09.588696v1.56","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1021\/bi00123a015","article-title":"Quantifying the allosteric properties of Escherichia coli carbamyl phosphate synthetase: determination of thermodynamic linked-function parameters in an ordered kinetic mechanism","volume":"31","year":"1992","journal-title":"Biochemistry"},{"key":"2024041108001094000_2024.04.09.588696v1.57","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8295-8"},{"key":"2024041108001094000_2024.04.09.588696v1.58","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.5.1667-1679.2006"},{"key":"2024041108001094000_2024.04.09.588696v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(68)90116-2"},{"key":"2024041108001094000_2024.04.09.588696v1.60","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1128\/jb.121.3.814-822.1975","article-title":"Control of expression of the pyr genes in Salmonella typhimurium: effects of variations in uridine and cytidine nucleotide pools","volume":"121","year":"1975","journal-title":"Journal of Bacteriology"},{"key":"2024041108001094000_2024.04.09.588696v1.61","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00001-08"},{"key":"2024041108001094000_2024.04.09.588696v1.62","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.6.3201-3207.1990"},{"key":"2024041108001094000_2024.04.09.588696v1.63","doi-asserted-by":"crossref","first-page":"21239","DOI":"10.1016\/S0021-9258(19)30072-9","article-title":"Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli","volume":"264","year":"1989","journal-title":"Journal of Biological Chemistry"},{"key":"2024041108001094000_2024.04.09.588696v1.64","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.4.2124-2127.1989"},{"key":"2024041108001094000_2024.04.09.588696v1.65","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1128\/jb.106.3.856-862.1971","article-title":"Effect of trimethoprim on macromolecular synthesis in Escherichia coli","volume":"106","year":"1971","journal-title":"Journal of Bacteriology"},{"key":"2024041108001094000_2024.04.09.588696v1.66","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1021\/cb100096f","article-title":"Antifolate-induced depletion of intracellular glycine and purines inhibits thymineless death in E. coli","volume":"5","year":"2010","journal-title":"ACS chemical biology"},{"key":"2024041108001094000_2024.04.09.588696v1.67","doi-asserted-by":"publisher","DOI":"10.1126\/science.1219192"},{"key":"2024041108001094000_2024.04.09.588696v1.68","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719627115"},{"key":"2024041108001094000_2024.04.09.588696v1.69","doi-asserted-by":"crossref","unstructured":"Y. Liu et al., Thymine sensitizes gram-negative pathogens to antibiotic killing. Frontiers in Microbiology 12, 622798 (2021).","DOI":"10.3389\/fmicb.2021.622798"},{"key":"2024041108001094000_2024.04.09.588696v1.70","first-page":"e00480","article-title":"Adenosine awakens metabolism to enhance growth-independent killing of tolerant and persister bacteria across multiple classes of antibiotics","volume":"13","year":"2022","journal-title":"MBio"},{"key":"2024041108001094000_2024.04.09.588696v1.71","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3390\/antibiotics4040627","article-title":"Genetic screen reveals the role of purine metabolism in Staphylococcus aureus persistence to rifampicin","volume":"4","year":"2015","journal-title":"Antibiotics"},{"key":"2024041108001094000_2024.04.09.588696v1.72","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00913-20"},{"key":"2024041108001094000_2024.04.09.588696v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.10.020"},{"key":"2024041108001094000_2024.04.09.588696v1.74","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00144-08"},{"key":"2024041108001094000_2024.04.09.588696v1.75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2010.00213.x"},{"key":"2024041108001094000_2024.04.09.588696v1.76","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01020-07"},{"key":"2024041108001094000_2024.04.09.588696v1.77","doi-asserted-by":"crossref","unstructured":"A. J. Lopatkin , J. H. Yang , Digital insights into nucleotide metabolism and antibiotic treatment failure. Frontiers in digital health 3, 583468 (2021).","DOI":"10.3389\/fdgth.2021.583468"},{"key":"2024041108001094000_2024.04.09.588696v1.78","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0274"},{"key":"2024041108001094000_2024.04.09.588696v1.79","doi-asserted-by":"publisher","DOI":"10.1186\/2193-1801-3-1"},{"key":"2024041108001094000_2024.04.09.588696v1.80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031252"},{"key":"2024041108001094000_2024.04.09.588696v1.81","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1751-7915.2008.00060.x","article-title":"Uracil influences quorum sensing and biofilm formation in Pseudomonas aeruginosa and fluorouracil is an antagonist","volume":"2","year":"2009","journal-title":"Microbial biotechnology"},{"key":"2024041108001094000_2024.04.09.588696v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(01)05321-1"},{"key":"2024041108001094000_2024.04.09.588696v1.83","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msz144"},{"key":"2024041108001094000_2024.04.09.588696v1.84","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00623-00619"},{"key":"2024041108001094000_2024.04.09.588696v1.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.05.007"},{"key":"2024041108001094000_2024.04.09.588696v1.86","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00965-1"},{"key":"2024041108001094000_2024.04.09.588696v1.87","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920013117"},{"key":"2024041108001094000_2024.04.09.588696v1.88","doi-asserted-by":"crossref","unstructured":"A. Salzer , D. Keinh\u00f6rster , C. K\u00e4stle , B. K\u00e4stle , C. Wolz , Small alarmone synthetases RelP and RelQ of Staphylococcus aureus are involved in biofilm formation and maintenance under cell wall stress conditions. Frontiers in Microbiology 11, 575882 (2020).","DOI":"10.3389\/fmicb.2020.575882"},{"key":"2024041108001094000_2024.04.09.588696v1.89","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1822026116"},{"key":"2024041108001094000_2024.04.09.588696v1.90","doi-asserted-by":"crossref","first-page":"563944","DOI":"10.3389\/fmicb.2020.563944","article-title":"(p) ppGpp metabolism and antimicrobial resistance in bacterial pathogens","volume":"11","year":"2020","journal-title":"Frontiers in Microbiology"},{"key":"2024041108001094000_2024.04.09.588696v1.91","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-018-03267-5"},{"key":"2024041108001094000_2024.04.09.588696v1.92","doi-asserted-by":"crossref","first-page":"e2213116119","DOI":"10.1073\/pnas.2213116119","article-title":"Repurposed dihydroorotate dehydrogenase inhibitors with efficacy against drug-resistant Acinetobacter baumannii","volume":"119","year":"2022","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"2024041108001094000_2024.04.09.588696v1.93","doi-asserted-by":"crossref","unstructured":"T. Baba et al., Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Molecular systems biology 2, 2006.0008-2006.0008 (2006).","DOI":"10.1038\/msb4100050"},{"key":"2024041108001094000_2024.04.09.588696v1.94","doi-asserted-by":"publisher","DOI":"10.1038\/ng1348"},{"key":"2024041108001094000_2024.04.09.588696v1.95","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41596-018-0098-2","article-title":"Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v. 3.0","volume":"14","year":"2019","journal-title":"Nature protocols"},{"key":"2024041108001094000_2024.04.09.588696v1.96","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3956"},{"key":"2024041108001094000_2024.04.09.588696v1.97","doi-asserted-by":"crossref","first-page":"e9913","DOI":"10.15252\/msb.20209913","article-title":"Conjugation dynamics depend on both the plasmid acquisition cost and the fitness cost","volume":"17","year":"2021","journal-title":"Molecular systems biology"},{"key":"2024041108001094000_2024.04.09.588696v1.98","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTZ931"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.04.09.588696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:15:29Z","timestamp":1768457729000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.04.09.588696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,9]]},"references-count":98,"URL":"https:\/\/doi.org\/10.1101\/2024.04.09.588696","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/spectrum.01895-24","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,4,9]]},"subtype":"preprint"}}