, RTB/NIAID) for help with graphics, and Taylor Robinson (RML/NIAID) for manuscript improvements and plagiarism checking

P. P. Adams, C. Flores-avile, N. Popitsch, I. Bilusic, R. Schroeder et al., In vivo expression technology and 5 end mapping of the Borrelia burgdorferi transcriptome identify novel RNAs expressed during mammalian infection, Nucleic Acids Res, vol.45, pp.775-792, 2017.

R. Amin, M. Franz-wachtel, Y. Tiffert, M. Heberer, M. Meky et al., Post-translational serine/threonine phosphorylation and lysine acetylation: a novel regulatory aspect of the global nitrogen response regulator glnR in S. coelicolor, M145. Front. Mol. Biosci, vol.3, p.38, 2016.

C. Angione, G. Carapezza, J. Costanza, P. Lio, and G. Nicosia, Pareto optimality in organelle energy metabolism analysis, IEEE/ACM Trans. Comput. Biol. Bioinform, vol.10, pp.1032-1044, 2013.

L. Archambault, J. S. Borchert, J. Bergeron, S. Snow, and P. J. Schlax, Measurements of mRNA degradation in Borrelia burgdorferi, J. Bacteriol, vol.195, pp.4879-4887, 2013.

L. Archambault, J. Linscott, N. Swerdlow, K. Boyland, E. Riley et al., Translational efficiency of rpoS mRNA from Borrelia burgdorferi: effects of the length and sequence of the mRNA leader region, Biochem. Biophys. Res. Commun, vol.433, pp.73-78, 2013.

A. G. Barbour, Isolation and cultivation of Lyme disease spirochetes, Yale J. Biol. Med, vol.57, pp.521-525, 1984.

A. G. Barbour, M. Adeolu, R. S. Gupta, and . Margos, Division of the genus Borrelia into two genera (corresponding to Lyme disease and relapsing fever groups) reflects their genetic and phenotypic distinctiveness and will lead to a better understanding of these two groups of microbes, Int. J. Syst. Evol. Microbiol, vol.67, pp.2058-2067, 2016.

A. G. Barbour, S. F. Hayes, R. A. Heiland, M. E. Schrumpf, and S. L. Tessier, A Borrelia-specific monoclonal antibody binds to a flagellar epitope, Infect. Immun, vol.52, pp.549-554, 1986.

V. Bernal, S. Castano-cerezo, J. Gallego-jara, A. Ecija-conesa, T. De-diego et al., Regulation of bacterial physiology by lysine acetylation of proteins, N. Biotechnol, vol.31, pp.586-595, 2014.

G. Bertani, Lysogeny at mid-twentieth century: P1, P2, and other experimental systems, J. Bacteriol, vol.186, pp.595-600, 2004.

S. A. Bhat, I. K. Iqbal, and A. Kumar, Imaging the NADH:NAD + homeostasis for understanding the metabolic response of mycobacterium to physiologically relevant stresses, Front. Cell. Infect. Microbiol, vol.6, p.145, 2016.

J. S. Blevins, H. Xu, M. He, M. V. Norgard, L. Reitzer et al., , 2009.

, Rrp2, a sigma54-dependent transcriptional activator of Borrelia burgdorferi, activates rpoS in an enhancer-independent manner, J. Bacteriol, vol.191, pp.2902-2905

W. Burgdorfer, A. G. Barbour, S. F. Hayes, J. L. Benach, E. Grunwaldt et al., Lyme disease-a tick-borne spirochetosis?, Science, vol.216, pp.1317-1319, 1982.

M. N. Burtnick, J. S. Downey, P. J. Brett, J. A. Boylan, J. G. Frye et al., Insights into the complex regulation of rpoS in Borrelia burgdorferi, Mol. Microbiol, vol.65, pp.277-293, 2007.

F. C. Cabello, H. P. Godfrey, J. V. Bugrysheva, and S. A. Newman, Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle, Environ. Microbiol, vol.19, pp.3846-3862, 2017.

M. J. Caimano, D. Drecktrah, F. Kung, and D. S. Samuels, Interaction of the Lyme disease spirochete with its tick vector, Cell. Microbiol, vol.18, pp.919-927, 2016.

M. J. Caimano, S. Dunham-ems, A. M. Allard, M. B. Cassera, M. Kenedy et al., Cyclic di-GMP modulates gene expression in Lyme disease spirochetes at the tick-mammal interface to promote spirochete survival during the blood meal and tick-to-mammal transmission, Infect. Immun, vol.83, pp.3043-3060, 2015.

J. A. Cain, N. Solis, and S. J. Cordwell, Beyond gene expression: the impact of protein post-translational modifications in bacteria, J. Proteomics, vol.97, pp.265-286, 2014.

V. J. Carabetta and I. M. Cristea, Regulation, function, and detection of protein acetylation in bacteria, J. Bacteriol, vol.199, pp.107-124, 2017.

S. Casjens, N. Palmer, R. Van-vugt, W. M. Huang, B. Stevenson et al., A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi, Mol. Microbiol, vol.35, pp.490-516, 2000.

S. Castano-cerezo, V. Bernal, H. Post, T. Fuhrer, S. Cappadona et al., Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli, Mol. Syst. Biol, vol.10, p.762, 2014.

H. A. Crosby, D. A. Pelletier, G. B. Hurst, and J. C. Escalante-semerena, System-wide studies of N-lysine acetylation in Rhodopseudomonas palustris reveal substrate specificity of protein acetyltransferases, J. Biol. Chem, vol.287, pp.15590-15601, 2012.

M. R. De-graef, S. Alexeeva, J. L. Snoep, and J. Teixeira-de-mattos, The steady-state internal redox state (NADH/NAD) reflects the external redox state and is correlated with catabolic adaptation in Escherichia coli, J. Bacteriol, vol.181, pp.2351-2357, 1999.

A. F. Elias, P. E. Stewart, D. Grimm, M. J. Caimano, C. H. Eggers et al., Clonal polymorphism of Borrelia burgdorferi strain B31 MI: implications for mutagenesis in an infectious strain background, Infect. Immun, vol.70, pp.2139-2150, 2002.

C. M. Fraser, S. Casjens, W. M. Huang, G. G. Sutton, R. Clayton et al., Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi, Nature, vol.390, pp.580-586, 1997.

J. G. Gardner and J. C. Escalante-semerena, Biochemical and mutational analyses of AcuA, the acetyltransferase enzyme that controls the activity of the acetyl coenzyme a synthetase (AcsA) in Bacillus subtilis, J. Bacteriol, vol.190, pp.5132-5136, 2008.

J. G. Gardner, F. J. Grundy, T. M. Henkin, and J. C. Escalante-semerena, Control of acetyl-coenzyme A synthetase (AcsA) activity by acetylation/deacetylation without NAD + involvement in Bacillus subtilis, J. Bacteriol, vol.188, pp.5460-5468, 2006.

F. C. Gherardini, J. A. Boylan, K. Lawrence, and J. Skare, Metabolism and physiology of Borrelia, Borrelia: Molecular Biology, Host Interaction and Pathogenesis, pp.103-138, 2010.

S. Ghosh, B. Padmanabhan, C. Anand, and V. Nagaraja, Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization, Mol. Microbiol, vol.100, pp.577-588, 2016.

M. A. Gilbert, E. A. Morton, S. F. Bundle, and D. S. Samuels, Artificial regulation of ospC expression in Borrelia burgdorferi, Mol. Microbiol, vol.63, pp.1259-1273, 2007.

J. D. Hayden, L. R. Brown, H. P. Gunawardena, E. F. Perkowski, X. Chen et al., Reversible acetylation regulates acetate and propionate metabolism in Mycobacterium smegmatis, Microbiology, vol.159, pp.1986-1999, 2013.

C. S. Henry, L. J. Broadbelt, and V. Hatzimanikatis, Thermodynamicsbased metabolic flux analysis, Biophys. J, vol.92, pp.1792-1805, 2007.

K. L. Hentchel and J. C. Escalante-semerena, Acylation of biomolecules in prokaryotes: a widespread strategy for the control of biological function and metabolic stress. Microbiol, Mol. Biol. Rev, vol.79, pp.321-346, 2015.

L. I. Hu, B. K. Chi, M. L. Kuhn, E. V. Filippova, A. J. Walker-peddakotla et al., Acetylation of the response regulator RcsB controls transcription from a small RNA promoter, J. Bacteriol, vol.195, pp.4174-4186, 2013.

L. I. Hu, B. P. Lima, and A. J. Wolfe, Bacterial protein acetylation: the dawning of a new age, Mol. Microbiol, vol.77, pp.15-21, 2010.

N. Hulo, A. Bairoch, V. Bulliard, L. Cerutti, B. A. Cuche et al., The 20 years of PROSITE, Nucleic Acids Res, vol.36, pp.245-249, 2008.

W. Humphrey, A. Dalke, and K. Schultenm, VMD -visual molecular dynamics, J. Mol. Graph, vol.14, pp.33-38, 1996.

M. Kafri, E. Metzl-raz, G. Jona, and N. Barkai, The cost of protein production, Cell Rep, vol.14, pp.22-31, 2016.

M. Kanehisa and S. Goto, KEGG: kyoto encyclopedia of genes and genomes, Nucleic Acids Res, vol.28, 2000.

J. L. Kostick, L. T. Szkotnicki, E. A. Rogers, P. Bocci, N. Raffaelli et al., The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes, Mol. Microbiol, vol.81, pp.219-231, 2011.

J. B. Lalanne, J. C. Taggart, M. S. Guo, L. Herzel, A. Schieler et al., Evolutionary convergence of pathway-specific enzyme expression stoichiometry, Cell, vol.173, 2018.

Q. Meng, P. Liu, J. Wang, Y. Wang, L. Hou et al., Systematic analysis of the lysine acetylome of the pathogenic bacterium Spiroplasma eriocheiris reveals acetylated proteins related to metabolism and helical structure, J. Proteomics, vol.148, pp.159-169, 2016.

E. S. Nakayasu, M. C. Burnet, H. E. Walukiewicz, C. S. Wilkins, A. K. Shukla et al., Ancient regulatory role of lysine acetylation in central metabolism, mBio, vol.8, pp.1894-1911, 2017.

E. A. Novak, S. Z. Sultan, and M. A. Motaleb, The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi. Front. Cell. Infect. Microbiol, vol.4, p.56, 2014.

T. Ouidir, T. Kentache, and J. Hardouin, Protein lysine acetylation in bacteria: current state of the art, Proteomics, vol.16, pp.301-309, 2016.

Z. Ouyang, J. S. Blevins, and M. V. Norgard, Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi, Microbiology, vol.156, pp.2641-2658, 2008.

R. Overbeek, N. Larsen, T. Walunas, M. Souza, G. Pusch et al., The ERGO genome analysis and discovery system, Nucleic Acids Res, vol.31, pp.164-171, 2003.

J. Ren, Y. Sang, J. Lu, and Y. F. Yao, Protein acetylation and its role in bacterial virulence, Trends Microbiol, vol.25, pp.768-779, 2017.

C. L. Richards, K. A. Lawrence, H. Su, Y. Yang, X. F. Yang et al., Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi, PLoS One, vol.10, p.144472, 2015.

E. A. Rogers, D. Terekhova, H. M. Zhang, K. M. Hovis, I. Schwartz et al., Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions, Mol. Microbiol, vol.71, pp.1551-1573, 2009.

D. S. Samuels, Electrotransformation of the spirochete Borrelia burgdorferi, Methods Mol. Biol, vol.47, pp.253-259, 1995.

Y. Sang, J. Ren, J. Ni, J. Tao, J. Lu et al., Protein Acetylation is involved in Salmonella enterica serovar Typhimurium virulence, J. Infect. Dis, vol.213, pp.1836-1845, 2016.

O. Shoval, H. Sheftel, G. Shinar, Y. Hart, O. Ramote et al., Evolutionary trade-offs, Pareto optimality, and the geometry of phenotype space, Science, vol.336, pp.1157-1160, 2012.

C. J. Sigrist, L. Cerutti, N. Hulo, A. Gattiker, L. Falquet et al., PROSITE: a documented database using patterns and profiles as motif descriptors, Brief. Bioinform, vol.3, pp.265-274, 2002.

C. J. Sigrist, E. De-castro, L. Cerutti, B. A. Cuche, N. Hulo et al., New and continuing developments at PROSITE, Nucleic Acids Res, vol.41, pp.344-347, 2013.

C. J. Sigrist, E. De-castro, P. S. Langendijk-genevaux, V. Le-saux, A. Bairoch et al., ProRule: a new database containing functional and structural information on PROSITE profiles, Bioinformatics, vol.21, pp.4060-4066, 2005.

J. L. Snoep, M. R. De-graef, M. J. Teixeira-de-mattos, and O. M. Neijssel, Effect of culture conditions on the NADH/NAD ratio and total amounts of NAD(H) in chemostat cultures of Enterococcus faecalis NCTC 775, FEMS Microbiol. Lett, vol.116, pp.263-267, 1994.

S. Y. Srivastava and A. M. Silva, Reciprocal expression of ospA and ospC in single cells of Borrelia burgdorferi, J. Bacteriol, vol.190, pp.3429-3433, 2008.

V. J. Starai, J. G. Gardner, and J. C. Escalante-semerena, Residue Leu-641 of Acetyl-CoA synthetase is critical for the acetylation of residue Lys-609 by the Protein acetyltransferase enzyme of Salmonella enterica, J. Biol. Chem, vol.280, pp.26200-26205, 2005.

A. C. Steere, R. L. Grodzicki, A. N. Kornblatt, J. E. Craft, A. G. Barbour et al., The spirochetal etiology of Lyme disease, N. Engl. J. Med, vol.308, pp.733-740, 1983.

J. Sterba, M. Vancova, N. Rudenko, M. Golovchenko, T. L. Tremblay et al., Flagellin and outer surface proteins from Borrelia burgdorferi are not glycosylated, J. Bacteriol, vol.190, pp.2619-2623, 2008.

P. E. Stewart and P. A. Rosa, Physiologic and genetic factors influencing the zoonotic cycle of Borrelia burgdorferi, Curr. Top. Microbiol. Immunol, 2017.

F. Sun, C. Dai, J. Xie, and X. Hu, Biochemical issues in estimation of cytosolic free NAD/NADH ratio, PLoS One, vol.7, p.34525, 2012.

P. Szekely, H. Sheftel, A. Mayo, A. , and U. , Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems, PLoS Comput. Biol, vol.9, p.1003163, 2013.

D. Szklarczyk, A. Franceschini, S. Wyder, K. Forslund, D. Heller et al., STRING v10: protein-protein interaction networks, integrated over the tree of life, Nucleic Acids Res, vol.43, pp.447-452, 2015.

M. Tanabe and M. Kanehisa, Using the KEGG database resource, Curr. Protoc. Bioinformatics, vol.1, 2012.

S. Thao and J. C. Escalante-semerena, Control of protein function by reversible Nvarepsilon-lysine acetylation in bacteria, Curr. Opin. Microbiol, vol.14, pp.200-204, 2011.

, UniProt: the universal protein knowledgebase, The UniProt Consortium, vol.45, 2017.

E. B. Troy, T. Lin, L. Gao, D. W. Lazinski, M. Lundt et al., Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi, Mol. Microbiol, vol.101, pp.1003-1023, 2016.

S. Tu, S. J. Guo, C. S. Chen, C. X. Liu, H. W. Jiang et al., YcgC represents a new protein deacetylase family in prokaryotes, vol.4, p.5322, 2015.

A. C. Tucker and J. C. Escalante-semerena, Acetoacetyl-CoA synthetase activity is controlled by a protein acetyltransferase with unique domain organization in Streptomyces lividans, Mol. Microbiol, vol.87, pp.152-167, 2013.

T. A. Van-laar, Y. H. Lin, C. L. Miller, S. L. Karna, J. P. Chambers et al., Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi, PLoS One, vol.7, p.38171, 2012.

S. Venkat, C. Gregory, J. Sturges, Q. Gan, F. et al., Studying the Lysine acetylation of malate dehydrogenase, J. Mol. Biol, vol.429, pp.1396-1405, 2017.

O. Vergnolle, H. Xu, J. M. Tufariello, L. Favrot, A. A. Malek et al., Post-translational acetylation of MbtA modulates mycobacterial siderophore biosynthesis, J. Biol. Chem, vol.291, pp.22315-22326, 2016.

J. A. Vizcaino, A. Csordas, N. Del-toro, J. A. Dianes, J. Griss et al., 2016 update of the PRIDE database and its related tools, Nucleic Acids Res, vol.44, pp.447-456, 2016.

K. Von-lackum and B. Stevenson, Carbohydrate utilization by the Lyme borreliosis spirochete, Borrelia burgdorferi, FEMS Microbiol. Lett, vol.243, pp.173-179, 2005.

G. R. Wagner and M. D. Hirschey, Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases, Mol. Cell, vol.54, pp.5-16, 2014.

A. J. Wolfe, Bacterial protein acetylation: new discoveries unanswered questions, Curr. Genet, vol.62, pp.335-341, 2016.

J. Yang, R. Yan, A. Roy, D. Xu, J. Poisson et al., The I-TASSER suite: protein structure and function prediction, Nat. Methods, vol.12, pp.7-8, 2015.

Y. Yang, A. Wolfe, Y. , and X. F. , Identification of Acetylated proteins in Borrelia burgdorferi, Methods Mol. Biol, vol.1690, pp.177-182, 2018.

Y. Zhang, I-TASSER server for protein 3D structure prediction, BMC Bioinformatics, vol.9, p.40, 2008.