A. C. Matin

Last updated
A. C. Matin
Born1941
Delhi, India
DiedApril 14, 2024
Stanford, CA
NationalityPakistani-American
EducationB.S., microbiology
M.S., microbiology
Ph.D., microbiology
Alma mater University of Karachi, Pakistan
University of California, Los Angeles
Occupation(s)Microbiologist, immunologist, and academician
AwardsElected fellow, American Academy of Microbiology
Elected Associate Fellow, Aerospace Medical Association
Recipient of NASA honor award for the ECAMSAT Project
Review Committee of the Accreditation Board for Engineering and Technology (ABET)
Academic career
Institutions Stanford University School of Medicine

A. C. Matin was a Pakistani-American microbiologist, immunologist, academician and researcher. He was a professor of microbiology and immunology at Stanford University School of Medicine. [1]

Contents

Matin published over 100 research papers plus several reviews and has many patents registered in his name. His research was focused on bio-molecular engineering, cellular resistance and virulence, drug discovery, biology of microgravity, bioremediation, stress promoters, stress sensing, and biotechnology. He made pioneering research contributions in biology and physiology of mixotrophy, starvation responses at the cellular and genetic levels, bacterial multidrug and biofilm resistance, role of G proteins in starvation and motility, discovery of an imageable cancer prodrug, specific drug targeting and the development of heritable contrast agent for molecular resonance imaging. Matin's work on antibiotic resistance along with his work as a principal investigator on E. coli AntiMicrobial Satellite (EcAMSat) system resulted in NASA sending E. coli to space for astronaut health protection in 2017. [2] He was the recipient of NASA honor award for the ECAMSAT Project.

Matin was the editor-in-chief of Open Access Journal of Applied Sciences.

Education

Matin studied microbiology at University of Karachi and received his bachelor's and master's degrees in 1960 and 1962, respectively, followed by college-level teaching for two years. He was awarded a Fulbright Fellowship, moved to the US and earned his Ph.D. in microbiology from University of California, Los Angeles in 1969. He completed his postdoctoral research from University of California in 1971. [1]

Career

Following his postdoctoral studies, Matin joined University of Groningen in the Netherlands as a first class scientific officer from 1971 till 1975 before moving back to the US and being appointed by Stanford University. He is a professor in Department of Microbiology and Immunology and is associated with Cancer Institute, Program in Genetic and Molecular Medicine, Woods Environmental Institute, [3] Cardiovascular Institute, Institute for Immunity, and BioX Program [4] at Stanford University. From 1989 till 1998 (when the program ended), he served as a professor at Western Region Hazardous Substance Research Center at the university. [1]

Research

Matin's work was focused on various microbiology and biotechnology related topics including antibiotic resistance, cancer research, bio-molecular engineering, biofilms, cellular resistance and virulence, biology of microgravity, bioremediation, stress promoters, stress sensing, and systems biology. His work in bioenergetics provided fundamental insights into how acidophilic bacteria, which grow at a pH of 3 or lower, keep a neutral cytoplasm. [5]

Enzyme improvement and targeted therapy for cancer research

Matin discovered a new gene delivered enzyme prodrug therapy consisting of CNOB, [6] and the enzyme ChrR which activates the CNOB. He then improved and humanized the enzyme to HChrR6 [7] by using non structure-based approaches like DNA shuffling; [8] a novel statistical method for protein improvement, [9] as well as analyzing HChrR structure. [10]

Matin found that the activated toxic product of CNOB, MCHB, is highly fluorescent [11] and used this discovery for the development of a method using mRNA for targeting the HChrR6 gene specifically to cancer. [12] He generated exosomes loaded with the HChrR6 mRNA that displayed high affinity anti-HER2 scFv, and named them EXODEPTs; the EXODEPTs specifically targeted the HER2 receptor and delivered the HChrR6 mRNA only to HER2-positive cells. [13] Matin applied systemic EXODEPT injection along with CNOB or tretazicar (CB1954), and found complete growth arrest of orthotopic HER2 positive breast cancer xenografts in mice without injuring other tissues or organs, indicating no off-target prodrug activation. This work was highlighted in Science Translational Medicine. [14] He was the pioneer in using exosomes to deliver exogenous mRNA. [13] [12] Matin also showed that magnetotactic bacteria can specifically target tumors in mice and generate both positive and negative magnetic resonance imaging signals, and thus provide a potential tool for improved MRI visualization; this was the first use of these bacteria for this purpose. [15]

Bacterial hunger response

Matin studied the effect of nutrient deprivation in bacteria, which is often experienced by them in the human body and the environment, [16] [17] [18] and worked on induction of two classes of starvation genes named as cyclic AMP-dependent and independent. [19] [20] [21] He studied the comprehensive resistant state of the bacteria. For example, hunger stress made bacteria more resistant not only to nutrient deprivation but also to oxidative stress, a major resistance mechanism in humans against pathogenic bacteria, as well as to heat and osmotic stresses. [20] [22] [23]

Matin pioneered the discovery that this comprehensive resistance was due to cAMP-independent class of proteins, called the Pex proteins, [21] further he showed that the Pex protein synthesis was controlled by σs (formerly called KatF) and that this sigma factor thereby controlled development of the general stress response. [24] Hunger stress was found to trigger the expression of virulence proteins in bacteria enhancing their pathogenic prowess. [25] [26]

Matin's work was instrumental in the discovery of σs and its regulation. [27] [28] His research also resulted in the first identification of the physiological role for ClpXP protease, and showed that σs is rapidly degraded in fast growing cells by this protease; the site in the σs protein targeted by this protease was also identified. [27]

Matin used bioreactors to generate simulated microgravity (SMG) on Earth, [29] and showed that uropathogenic Escherichia coli (UPEC) developed σs-dependent comprehensive resistance under SMG, indicating that microgravity constitutes a stress. [30] He also studied protein folding and overproduced DnaK in an E. coil strain making the human growth hormone (HGH). His experiment resulted in much greater amount of normal and soluble HGH. [31]

Antibiotic resistance

Matin conducted research on the bacterial antibiotic resistance along with the threat of multidrug resistance (MDR) pumps in public health. His work indicated the regulation of the MDR pump by emrRAB operon and the EmrR protein. [32] [33] He found that the antibiotics alter the EmrR and prevent its binding to the promoter which leads to the synthesis of the pump and MDR. [33] He also showed that EmrR induces of the mcb operon protecting bacteria against additional antibiotics (e.g., fluoroquinolones). [34]

Matin discovered the mechanism of bactericidal antibiotics for generating oxidative stress. [18] His research indicated that suppressing UPEC antioxidant defense can bolster gentamicin (Gm) effectiveness In treating cystitis. He also studied the effects of σs-mediated enhanced resistance and SMG. [35] [36] Based on these studies, Matin in collaboration with NASA, designed a payload system for testing the effect of space microgravity on UPEC Gm resistance and confirmed that silencing of σs will make Gm more effective against bacterial infections also in space flight, [37] [38] providing the means of increasing Gm effectiveness both on Earth and space.

Matin focused on bacterial biofilms as a challenge in disease treatment. He used his discovery that E. coli strains fluoresce upon tetracycline treatment to test if biofilm penetration barrier accounted for their enhanced resistance. Tetracycline caused cells to fluoresce throughout the biofilms indicating no role for the penetration barrier. [39] However, a UPEC mutant missing the rapA gene, generated by Matin, showed that impaired penetration had a role in biofilm resistance to penicillin, norfloxacin, chloramphenicol, and Gm, and that, in addition, the yhcQ gene, which encoded a putative MDR pump was also involved. [40] That biofilm resistance differ for different antibiotics and different bacteria is now widely accepted.

Molecular bioremediation

Matin also studied bacterial bioremediation of the carcinogens chromate Cr(VI) and uranyl U(VI), which are wide-spread environmental pollutants, especially in the Department of Energy waste sites, [41] and worked on their bioremediation to the insoluble and nontoxic Cr(III) and U(IV). He studied various consequences after the bacterial exposure to chromate and uranyl, and found that the post-exposure effects resulted in one electron reduction of these carcinogens, generating the radicals Cr and U(V) by flavoproteins with various essential metabolic functions. These radicals interacted with oxygen, and generated large quantities of ROS by redox cycling, poisoning the bacteria. [42] [43]

Matin discovered a new class of enzymes, such as ChrR of E. coli, which are obligatory two-/four-electron reducers; these pre-empted the generation of the radicals. He then improved these enzymes and engineered bacteria more effective in remediating these carcinogens. [44] He also studied the physiological role of ChrR, which is to convert quinones to hydroxyquinones in one step, thus preventing the formation of semiquinones, which also redox cycle. In addition, this enzyme prevents redox cycling of numerous compounds generated during metabolism within the bacteria, and those present in the environment that have the proclivity for one-electron reduction.

Awards and honors

Bibliography


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  2. Tabor, Abigail (November 16, 2017). "NASA Is Sending E. coli to Space for Astronaut Health". NASA.
  3. "AC Matin". Stanford Woods Institute for the Environment. June 21, 2018.
  4. "A. C. Matin - Professor of Microbiology and Immunology". Welcome to Bio-X. March 7, 2014.
  5. "Ion Transport in Acidophiles" (PDF).
  6. Thorne, S. H.; Barak, Y.; Liang, W.; Bachmann, M. H.; Rao, J.; Contag, C. H.; Matin, A. (2009). "Europe PMC". Molecular Cancer Therapeutics. 8 (2): 333–341. doi:10.1158/1535-7163.MCT-08-0707. PMC   2670992 . PMID   19190118.
  7. Barak Y, Thorne SH, Ackerley DF, Lynch SV, Contag CH, Matin A (January 2006). "New enzyme for reductive cancer chemotherapy, YieF, and its improvement by directed evolution". Molecular Cancer Therapeutics. 5 (1): 97–103. doi: 10.1158/1535-7163.MCT-05-0365 . PMID   16432167.
  8. Barak Y, Ackerley DF, Dodge CJ, Banwari L, Alex C, Francis AJ, Matin A (November 2006). "Analysis of novel soluble chromate and uranyl reductases and generation of an improved enzyme by directed evolution". Applied and Environmental Microbiology. 72 (11): 7074–82. Bibcode:2006ApEnM..72.7074B. doi:10.1128/AEM.01334-06. PMC   1636143 . PMID   17088379.
  9. Barak Y, Nov Y, Ackerley DF, Matin A (February 2008). "Enzyme improvement in the absence of structural knowledge: a novel statistical approach". The ISME Journal. 2 (2): 171–9. Bibcode:2008ISMEJ...2..171B. doi: 10.1038/ismej.2007.100 . PMID   18253133.
  10. Eswaramoorthy S, Poulain S, Hienerwadel R, Bremond N, Sylvester MD, Zhang YB, et al. (April 27, 2012). "Crystal structure of ChrR--a quinone reductase with the capacity to reduce chromate". PLOS ONE. 7 (4): e36017. Bibcode:2012PLoSO...736017E. doi: 10.1371/journal.pone.0036017 . PMC   3338774 . PMID   22558308.
  11. Wang JH, Endsley AN, Green CE, Matin AC (July 2016). "Utilizing native fluorescence imaging, modeling and simulation to examine pharmacokinetics and therapeutic regimen of a novel anticancer prodrug". BMC Cancer. 16 (1): 524. doi: 10.1186/s12885-016-2508-6 . PMC   4960810 . PMID   27457630.
  12. 1 2 Forterre AV, Wang JH, Delcayre A, Kim K, Green C, Pegram MD, et al. (March 2020). "Extracellular Vesicle-Mediated In Vitro Transcribed mRNA Delivery for Treatment of HER2+ Breast Cancer Xenografts in Mice by Prodrug CB1954 without General Toxicity". Molecular Cancer Therapeutics. 19 (3): 858–867. doi: 10.1158/1535-7163.MCT-19-0928 . PMC   7056535 . PMID   31941722.
  13. 1 2 Wang JH, Forterre AV, Zhao J, Frimannsson DO, Delcayre A, Antes TJ, et al. (May 2018). "Anti-HER2 scFv-Directed Extracellular Vesicle-Mediated mRNA-Based Gene Delivery Inhibits Growth of HER2-Positive Human Breast Tumor Xenografts by Prodrug Activation". Molecular Cancer Therapeutics. 17 (5): 1133–1142. doi: 10.1158/1535-7163.MCT-17-0827 . PMC   5932266 . PMID   29483213.
  14. Jay, Steven M. (March 21, 2018). "An EVolving approach to directed enzyme prodrug therapy for cancer". Science Translational Medicine . 10 (433): eaat1642. doi:10.1126/scitranslmed.aat1642. S2CID   13682809.
  15. Benoit MR, Mayer D, Barak Y, Chen IY, Hu W, Cheng Z, et al. (August 2009). "Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria". Clinical Cancer Research. 15 (16): 5170–7. doi: 10.1158/1078-0432.CCR-08-3206 . PMC   3409839 . PMID   19671860.
  16. Matin A, Veldkamp H (April 1978). "Physiological basis of the selective advantage of a Spirillum sp. in a carbon-limited environment". Journal of General Microbiology. 105 (2): 187–97. doi: 10.1099/00221287-105-2-187 . PMID   641523.
  17. Matin, A.; Grootjans, A.; Hogenhuis, H. (1976). "Influence of dilution rate on enzymes of intermediary metabolism in two freshwater bacteria grown in continuous culture" (PDF). Journal of General Microbiology. 94 (2): 323–332. doi: 10.1099/00221287-94-2-323 . PMID   950555. S2CID   29754140.
  18. 1 2 Wang, Jing-Hung; Singh, Rachna; Benoit, Michael; Keyhan, Mimi; Sylvester, Matthew; Hsieh, Michael; Thathireddy, Anuradha; Hsieh, Yi-Ju; Matin, A. C. (October 1, 2014). "Sigma S-Dependent Antioxidant Defense Protects Stationary-Phase Escherichia coli against the Bactericidal Antibiotic Gentamicin". Antimicrobial Agents and Chemotherapy. 58 (10): 5964–5975. doi: 10.1128/AAC.03683-14 . PMC   4187989 . PMID   25070093.
  19. Groat, R. G.; Schultz, J. E.; Zychlinsky, E.; Bockman, A.; Matin, A. (November 1, 1986). "Starvation proteins in Escherichia coli: kinetics of synthesis and role in starvation survival". Journal of Bacteriology. 168 (2): 486–493. doi: 10.1128/jb.168.2.486-493.1986 . PMC   213508 . PMID   3536847.
  20. 1 2 Reeve, C. A.; Amy, P. S.; Matin, A. (December 1, 1984). "Role of protein synthesis in the survival of carbon-starved Escherichia coli K-12". Journal of Bacteriology. 160 (3): 1041–1046. doi:10.1128/JB.160.3.1041-1046.1984. PMC   215816 . PMID   6389505.
  21. 1 2 Schultz, J. E.; Latter, G. I.; Matin, A. (September 1, 1988). "Differential regulation by cyclic AMP of starvation protein synthesis in Escherichia coli". Journal of Bacteriology. 170 (9): 3903–3909. doi: 10.1128/jb.170.9.3903-3909.1988 . PMC   211388 . PMID   2842291.
  22. Jenkins, D. E.; Schultz, J. E.; Matin, A. (1988). "Starvation-induced cross protection against heat or H2O2 challenge in Escherichia coli". Journal of Bacteriology. 170 (9): 3910–3914. doi:10.1128/jb.170.9.3910-3914.1988. PMC   211389 . PMID   3045081.
  23. Jenkins, D. E.; Chaisson, S. A.; Matin, A. (1990). "Starvation-induced cross protection against osmotic challenge in Escherichia coli". Journal of Bacteriology. 172 (5): 2779–2781. doi:10.1128/jb.172.5.2779-2781.1990. PMC   208926 . PMID   2185233.
  24. McCann, M. P.; Kidwell, J. P.; Matin, A. (1991). "The putative sigma factor KatF has a central role in development of starvation-mediated general resistance in Escherichia coli". Journal of Bacteriology. 173 (13): 4188–4194. doi:10.1128/jb.173.13.4188-4194.1991. PMC   208069 . PMID   2061293.
  25. "Stress, Bacterial:General and Specific. Reference Module in Biomedical Science" (PDF).
  26. Sonenshein AL (April 2005). "CodY, a global regulator of stationary phase and virulence in Gram-positive bacteria". Current Opinion in Microbiology. 8 (2): 203–7. doi:10.1016/j.mib.2005.01.001. PMID   15802253.
  27. 1 2 Schweder, T.; Lee, K. H.; Lomovskaya, O.; Matin, A. (January 1, 1996). "Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease". Journal of Bacteriology. 178 (2): 470–476. doi: 10.1128/jb.178.2.470-476.1996 . PMC   177680 . PMID   8550468.
  28. Matin, A. (1991). "The molecular basis of carbon-starvation-induced general resistance in Escherichia coli". Molecular Microbiology. 5 (1): 3–10. doi:10.1111/j.1365-2958.1991.tb01819.x. PMID   2014002. S2CID   12518946.
  29. Lynch, S. V.; Brodie, E. L.; Matin, A. (December 16, 2004). "Role and Regulation of σs in General Resistance Conferred by Low-Shear Simulated Microgravity in Escherichia coli". Journal of Bacteriology. 186 (24): 8207–8212. doi: 10.1128/JB.186.24.8207-8212.2004 . PMC   532419 . PMID   15576768.
  30. Singh, Rachna; Matin, A. C. (April 16, 2016). Nickerson, Cheryl A.; Pellis, Neal R.; Ott, C. Mark (eds.). Effect of Spaceflight and Spaceflight Analogue Culture on Human and Microbial Cells: Novel Insights into Disease Mechanisms. Springer. pp. 259–282. doi:10.1007/978-1-4939-3277-1_13.
  31. Blum, Paul; Velligan, Mark; Lin, Norman; Matin, Abdul (1992). "DnaK-Mediated Alterations in Human Growth Hormone Protein Inclusion Bodies". Nature Biotechnology. 10 (3): 301–304. doi:10.1038/nbt0392-301. PMID   1369475. S2CID   2467334.
  32. Xiong, A.; Gottman, A.; Park, C.; Baetens, M.; Pandza, S.; Matin, A. (October 1, 2000). "The EmrR Protein Represses the Escherichia coli emrRAB Multidrug Resistance Operon by Directly Binding to Its Promoter Region". Antimicrobial Agents and Chemotherapy. 44 (10): 2905–2907. doi: 10.1128/AAC.44.10.2905-2907.2000 . PMC   90178 . PMID   10991887.
  33. 1 2 Lomovskaya, O.; Lewis, K.; Matin, A. (May 1, 1995). "EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB". Journal of Bacteriology. 177 (9): 2328–2334. doi: 10.1128/jb.177.9.2328-2334.1995 . PMC   176888 . PMID   7730261.
  34. Lomovskaya, O.; Kawai, F.; Matin, A. (1996). "Differential regulation of the mcb and emr operons of Escherichia coli: role of mcb in multidrug resistance". Antimicrobial Agents and Chemotherapy. 40 (4): 1050–1052. doi:10.1128/AAC.40.4.1050. PMC   163261 . PMID   8849229.
  35. Lynch, S. V.; Mukundakrishnan, K.; Benoit, M. R.; Ayyaswamy, P. S.; Matin, A. (December 1, 2006). "Escherichia coli Biofilms Formed under Low-Shear Modeled Microgravity in a Ground-Based System". Applied and Environmental Microbiology. 72 (12): 7701–7710. Bibcode:2006ApEnM..72.7701L. doi: 10.1128/AEM.01294-06 . PMC   1694224 . PMID   17028231.
  36. Matin, A.C.; Wang, J.-H.; Keyhan, Mimi; Singh, Rachna; Benoit, Michael; Parra, Macarena P.; Padgen, Michael R.; Ricco, Antonio J.; Chin, Matthew; Friedericks, Charlie R.; Chinn, Tori N.; Cohen, Aaron; Henschke, Michael B.; Snyder, Timothy V.; Lera, Matthew P.; Ross, Shannon S.; Mayberry, Christina M.; Choi, Sungshin; Wu, Diana T.; Tan, Ming X.; Boone, Travis D.; Beasley, Christopher C.; Piccini, Matthew E.; Spremo, Stevan M. (November 1, 2017). "Payload hardware and experimental protocol development to enable future testing of the effect of space microgravity on the resistance to gentamicin of uropathogenic Escherichia coli and its σs-deficient mutant". Life Sciences in Space Research. 15: 1–10. Bibcode:2017LSSR...15....1M. doi:10.1016/j.lssr.2017.05.001. PMID   29198308.
  37. Padgen, Michael R.; Lera, Matthew P.; Parra, Macarena P.; Ricco, Antonio J.; Chin, Matthew; Chinn, Tori N.; Cohen, Aaron; Friedericks, Charlie R.; Henschke, Michael B.; Snyder, Timothy V.; Spremo, Stevan M.; Wang, Jing-Hung; Matin, A.C. (February 1, 2020). "EcAMSat spaceflight measurements of the role of σs in antibiotic resistance of stationary phase Escherichia coli in microgravity". Life Sciences in Space Research. 24: 18–24. Bibcode:2020LSSR...24...18P. doi: 10.1016/j.lssr.2019.10.007 . PMID   31987476.
  38. "Payload hardware and experimental protocol development to enable future testing of the effect of space microgravity on the resistance to gentamicin of uropathogenic Escherichia coli and its σs-deficient mutant" (PDF).
  39. Stone, G.; Wood, P.; Dixon, L.; Keyhan, M.; Matin, A. (August 16, 2002). "Tetracycline Rapidly Reaches All the Constituent Cells of Uropathogenic Escherichia coli Biofilms". Antimicrobial Agents and Chemotherapy. 46 (8): 2458–2461. doi: 10.1128/AAC.46.8.2458-2461.2002 . PMC   127323 . PMID   12121918.
  40. Lynch, S. V.; Dixon, L.; Benoit, M. R.; Brodie, E. L.; Keyhan, M.; Hu, P.; Ackerley, D. F.; Andersen, G. L.; Matin, A. (October 1, 2007). "Role of the rapA Gene in Controlling Antibiotic Resistance of Escherichia coli Biofilms". Antimicrobial Agents and Chemotherapy. 51 (10): 3650–3658. doi: 10.1128/AAC.00601-07 . PMC   2043260 . PMID   17664315.
  41. "Targets of Improvement in Bacterial Chromate Bioremediation" (PDF).
  42. Ackerley, D. F.; Gonzalez, C. F.; Keyhan, M.; Blake, R.; Matin, A. (2004). "Mechanism of chromate reduction by the Escherichia coli protein, NfsA, and the role of different chromate reductases in minimizing oxidative stress during chromate reduction". Environmental Microbiology. 6 (8): 851–860. Bibcode:2004EnvMi...6..851A. doi:10.1111/j.1462-2920.2004.00639.x. PMID   15250887.
  43. Ackerley, D. F.; Barak, Y.; Lynch, S. V.; Curtin, J.; Matin, A. (May 16, 2006). "Effect of chromate stress on Escherichia coli K-12". Journal of Bacteriology. 188 (9): 3371–3381. doi:10.1128/JB.188.9.3371-3381.2006. PMC   1447458 . PMID   16621832.
  44. Gonzalez, Claudio F.; Ackerley, David F.; Lynch, Susan V.; Matin, A. (June 17, 2005). "ChrR, a Soluble Quinone Reductase of Pseudomonas putida That Defends against H2O2*". Journal of Biological Chemistry. 280 (24): 22590–22595. doi: 10.1074/jbc.M501654200 . PMID   15840577.
  45. "Editorial Board". London Journals Press.

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Bifunctional (p)ppGpp synthase/hydrolase SpoT or SpoT is a regulatory enzyme in the RelA/SpoT Homologue (RSH) protein family that synthesizes and hydrolyzes (p)ppGpp to regulate the bacterial stringent response to environmental stressors. SpoT is considered a "long" form RSH protein and is found in many bacteria and plant chloroplasts. SpoT and its homologues have been studied in bacterial model organism E.coli for their role in the production and degradation of (p)ppGpp in the stringent response pathway.

Roberto Kolter is Professor of Microbiology, Emeritus at Harvard Medical School, an author, and past president of the American Society for Microbiology. Kolter has been a professor at Harvard Medical School since 1983 and was Co-director of Harvard's Microbial Sciences Initiative from 2003-2018. During the 35-year term of the Kolter laboratory from 1983 to 2018, more than 130 graduate student and postdoctoral trainees explored an eclectic mix of topics gravitating around the study of microbes. Kolter is a fellow of the American Association for the Advancement of Science and of the American Academy of Microbiology.

Bacterial small RNAs are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.

<span class="mw-page-title-main">Toxin-antitoxin system</span> Biological process

A toxin-antitoxin system consists of a "toxin" and a corresponding "antitoxin", usually encoded by closely linked genes. The toxin is usually a protein while the antitoxin can be a protein or an RNA. Toxin-antitoxin systems are widely distributed in prokaryotes, and organisms often have them in multiple copies. When these systems are contained on plasmids – transferable genetic elements – they ensure that only the daughter cells that inherit the plasmid survive after cell division. If the plasmid is absent in a daughter cell, the unstable antitoxin is degraded and the stable toxic protein kills the new cell; this is known as 'post-segregational killing' (PSK).

<span class="mw-page-title-main">Plasmid-mediated resistance</span> Antibiotic resistance caused by a plasmid

Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit the plasmid during cell division. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially family Enterobacteriaceae. The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.

Thymineless death is the phenomenon by which bacteria, yeasts and mammalian cells undergo cell death when they are starved of thymidine triphosphate (dTTP), an essential precursor for DNA replication. This phenomenon underlies the mechanism of action of several antibacterial, antimalarial and anticancer agents, such as trimethoprim, sulfamethoxazole, methotrexate and fluorouracil.

Pathogenic <i>Escherichia coli</i> Strains of E. coli that can cause disease

Escherichia coli is a gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans. Unlike normal flora E. coli, the pathogenic varieties produce toxins and other virulence factors that enable them to reside in parts of the body normally not inhabited by E. coli, and to damage host cells. These pathogenic traits are encoded by virulence genes carried only by the pathogens.

<span class="mw-page-title-main">Universal stress protein</span>

The universal stress protein (USP) domain is a superfamily of conserved genes which can be found in bacteria, archaea, fungi, protozoa and plants. Proteins containing the domain are induced by many environmental stressors such as nutrient starvation, drought, extreme temperatures, high salinity, and the presence of uncouplers, antibiotics and metals.

<span class="mw-page-title-main">Curli</span> A proteinaceous extracellular fiber produced by enteric bacteria

The Curli protein is a type of amyloid fiber produced by certain strains of enterobacteria. They are extracellular fibers located on bacteria such as E. coli and Salmonella spp. These fibers serve to promote cell community behavior through biofilm formation in the extracellular matrix. Amyloids are associated with several human neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and prion diseases. The study of curli may help to understand human diseases thought to arise from improper amyloid fiber formation. The curli pili are generally assembled through the extracellular nucleation precipitation pathway.

<span class="mw-page-title-main">Pho regulon</span> Phosphate regulatory mechanism in cells

The Phosphate (Pho) regulon is a regulatory mechanism used for the conservation and management of inorganic phosphate within the cell. It was first discovered in Escherichia coli as an operating system for the bacterial strain, and was later identified in other species. The Pho system is composed of various components including extracellular enzymes and transporters that are capable of phosphate assimilation in addition to extracting inorganic phosphate from organic sources. This is an essential process since phosphate plays an important role in cellular membranes, genetic expression, and metabolism within the cell. Under low nutrient availability, the Pho regulon helps the cell survive and thrive despite a depletion of phosphate within the environment. When this occurs, phosphate starvation-inducible (psi) genes activate other proteins that aid in the transport of inorganic phosphate.