细菌附属敏感性：优化药物治疗的新思路

doi:10.11843/j.issn.0366-6964.2022.10.005

摘要/Abstract

摘要： 交叉耐药性（cross resistance）是指细菌耐药性进化过程中，对单一药物产生耐药性的同时，也会对结构或作用机理相似的药物产生耐药性的现象。附属敏感性（collateral sensitivity）则指细菌对某一药物敏感性下降时，反而对其他药物敏感性提高的现象。在抗菌药物的持续压力下，细菌会选择性地发生交叉耐药性或附属敏感性两种不同的进化路径。在后抗生素来临的时代背景下，科学家提出了一种新颖的治疗思路：借用细菌对药物的附属敏感性特征进行治疗方案的设计或优化。然而，细菌附属敏感性进化是极为复杂的过程，其发生概率不稳定且规律性不强。为更好地认知细菌附属敏感性的进化规律及应用前景，本文对影响细菌附属敏感性的关键因素及附属敏感性的产生规律进行综述，并以此提出目前研究的不足以及未来发展的可能方向。

关键词: 细菌耐药性, 附属敏感性, 耐药性进化

Abstract: “Cross resistance” (CR) is a phenomenon in which the bacteria have evolved to resist different types of antimicrobial molecules with similar structure or mechanisms of action, while "collateral sensitivity" (CS) can be defined as a situation where the bacteria have developed resistance to one antibiotic showed increased susceptibility to another antibiotic. The evolution of bacterial resistance is a complicated process that can either lead to cross resistance or collateral sensitivity under the selection pressure from antibiotics. Recently, CS has been proposed as a promising alternative approach to counteract the rising problem of antibiotic resistance. To better understand the mechanisms by which bacterial collateral sensitivity has been evolved and the application prospect of CS, in this review, we summarized our current knowledges on key factors influencing the bacterial collateral sensitivity and the regularities of CS. We also discuss directions and challenges for developing CS-informed treatment strategies.

Key words: bacteria resistance, collateral sensitivity, drug revolution resistance

中图分类号:

S859.7

黄颖然, 叶欣晴, 刘娟, 于洋. 细菌附属敏感性：优化药物治疗的新思路[J]. 畜牧兽医学报, 2022, 53(10): 3316-3325.

HUANG Yingran,YE Xinqing,LIU Juan,YU Yang. Bacterial Collateral Sensitivity:A New Perspective to Optimize Treatments[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(10): 3316-3325.

参考文献 63

[1]	ESTERLY J S, WAGNER J, MCLAUGHLIN M M, et al. Evaluation of clinical outcomes in patients with bloodstream infections due to gram-negative bacteria according to carbapenem MIC stratification[J]. Antimicrob Agents Chemother, 2012, 56(9):4885-4890.
[2]	LAXMINARAYAN R. Antibiotic effectiveness:balancing conservation against innovation[J]. Science, 2014, 345(6202):1299-1301.
[3]	IMAMOVIC L, SOMMER M O A. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development[J]. Sci Transl Med, 2013, 5(204):204ra132.
[4]	LÁZÁR V, SINGH G P, SPOHN R, et al. Bacterial evolution of antibiotic hypersensitivity[J]. Mol Syst Biol, 2013, 9(1):700.
[5]	PÁL C, PAPP B, LÁZÁR V. Collateral sensitivity of antibiotic-resistant microbes[J]. Trends Microbiol, 2015, 23(7):401-407.
[6]	BAYM M, STONE L K, KISHONY R. Multidrug evolutionary strategies to reverse antibiotic resistance[J]. Science, 2016, 351(6268):eaad3292.
[7]	ZHAO B Y, SEDLAK J C, SRINIVAS R, et al. Exploiting temporal collateral sensitivity in tumor clonal evolution[J]. Cell, 2016, 165(1):234-246.
[8]	IMAMOVIC L, ELLABAAN M M H, MACHADO A M D, et al. Drug-driven phenotypic convergence supports rational treatment strategies of chronic infections[J]. Cell, 2018, 172(1-2):121-134.
[9]	DHAWAN A, NICHOL D, KINOSE F, et al. Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer[J]. Sci Rep, 2017, 7(1):1232.
[10]	JENSEN P B, HOLM B, SORENSEN M, et al. In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines:preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin[J]. Br J Cancer, 1997, 75(6):869-877.
[11]	PLUCHINO K M, HALL M D, GOLDSBOROUGH A S, et al. Collateral sensitivity as a strategy against cancer multidrug resistance[J]. Drug Resist Updat, 2012, 15(1-2):98-105.
[12]	WANG L Q, DE OLIVEIRA R L, HUIJBERTS S, et al. An acquired vulnerability of drug-resistant melanoma with therapeutic potential[J]. Cell, 2018, 173(6):1413-1425.
[13]	KIM S, LIEBERMAN T D, KISHONY R. Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance[J]. Proc Natl Acad Sci U S A, 2014, 111(40):14494-14499.
[14]	NICHOL D, RUTTER J, BRYANT C, et al. Antibiotic collateral sensitivity is contingent on the repeatability of evolution[J]. Nat Commun, 2019, 10(1):334.
[15]	HERENCIAS C, RODRÍGUEZ-BELTRÁN J, LEÓN-SAMPEDRO R, et al. Collateral sensitivity associated with antibiotic resistance plasmids[J]. eLife, 2021, 10:e65130
[16]	ROSENKILDE C E H, MUNCK C, PORSE A, et al. Collateral sensitivity constrains resistance evolution of the CTX-M-15 β-lactamase[J]. Nat Commun, 2019, 10(1):618.
[17]	ROEMHILD R, ANDERSSON D I. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics[J]. PLoS Pathog, 2021, 17(1):e1009172.
[18]	KNOPP M, ANDERSSON D I. Predictable phenotypes of antibiotic resistance mutations[J]. mBio, 2018, 9(3):e00770-18.
[19]	ANDERSSON D I, HUGHES D. Antibiotic resistance and its cost:is it possible to reverse resistance?[J]. Nat Rev Microbiol, 2010, 8(4):260-271.
[20]	VOGWILL T, KOJADINOVIC M, MACLEAN R C. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas[J]. Proc Biol Sci, 2016, 283(1830):20160151.
[21]	BENNETT A F, LENSKI R E. An experimental test of evolutionary trade-offs during temperature adaptation[J]. Proc Natl Acad Sci U S A, 2007, 104(S1):8649-8654.
[22]	VELICER G J, SCHMIDT T M, LENSKI R E. Application of traditional and phylogenetically based comparative methods to test for a trade-off in bacterial growth rate at low versus high substrate concentration[J]. Microb Ecol, 1999, 38(3):191-200.
[23]	PALMER A C, KISHONY R. Opposing effects of target overexpression reveal drug mechanisms[J]. Nat Commun, 2014, 5(1):4296.
[24]	TOPRAK E, VERES A, MICHEL J B, et al. Evolutionary paths to antibiotic resistance under dynamically sustained drug selection[J]. Nat Genet, 2012, 44(1):101-105.
[25]	LÁZÁR V, NAGY I, SPOHN R, et al. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network[J]. Nat Commun, 2014, 5(1):4352.
[26]	DRAGOSITS M, MOZHAYSKIY V, QUINONES-SOTO S, et al. Evolutionary potential, cross-stress behavior and the genetic basis of acquired stress resistance in Escherichia coli[J]. Mol Syst Biol, 2013, 9:643.
[27]	OSHIMA T, AIBA H, MASUDA Y, et al. Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12[J]. Mol Microbiol, 2002, 46(1):281-291.
[28]	VENKATESH B, BABUJEE L, LIU H, et al. The Erwinia chrysanthemi 3937 PhoQ sensor kinase regulates several virulence determinants[J]. J Bacteriol, 2006, 188(8):3088-3098.
[29]	ROEMHILD R, LINKEVICIUS M, ANDERSSON D I. Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin[J]. PLoS Biol, 2020, 18(1):e3000612.
[30]	BRYANT D W, MCCALLA D R. Nitrofuran induced mutagenesis and error prone repair in Escherichia coli[J]. Chem-Biol Interact, 1980, 31(2):151-166.
[31]	HUISMAN O, D'ARI R. An inducible DNA replication-cell division coupling mechanism in E. coli[J]. Nature, 1981, 290(5809):797-799.
[32]	BI E, LUTKENHAUS J. Cell division inhibitors SulA and MinCD prevent formation of the FtsZ ring[J]. J Bacteriol, 1993, 175(4):1118-1125.
[33]	MIZUSAWA S, GOTTESMAN S. Protein degradation in Escherichia coli:The lon gene controls the stability of sulA protein[J]. Proc Natl Acad Sci U S A, 1983, 80(2):358-362.
[34]	AULIN L B S, LIAKOPOULOS A, VAN DER GRAAF P H, et al. Design principles of collateral sensitivity-based dosing strategies[J]. Nat Commun, 2021, 12(1):5691.
[35]	ARDELL S M, KRYAZHIMSKIY S. The population genetics of collateral resistance and sensitivity[J]. eLife, 2021, 10:e73250.
[36]	APJOK G, BOROSS G, NYERGES Á, et al. Limited evolutionary conservation of the phenotypic effects of antibiotic resistance mutations[J]. Mol Biol Evol, 2019, 36(8):1601-1611.
[37]	CHEN H L, JIANG Y, LI M M, et al. Acquisition of tigecycline resistance by carbapenem-resistant Klebsiella pneumoniae confers collateral hypersensitivity to aminoglycosides[J]. Front Microbiol, 2021, 12:674502.
[38]	GAGNEUX S, LONG C D, SMALL P M, et al. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis[J]. Science, 2006, 312(5782):1944-1946.
[39]	RODRíGUEZ-ROJAS A, MACIÁ M D, COUCE A, et al. Assessing the emergence of resistance:the absence of biological cost in vivo may compromise fosfomycin treatments for P. Aeruginosa infections[J]. PLoS One, 2010, 5(4):e10193.
[40]	BJOÖRKMAN J, NAGAEV I, BERG O G, et al. Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance[J]. Science, 2000, 287(5457):1479-1482.
[41]	MAISNIER-PATIN S, PAULANDER W, PENNHAG A, et al. Compensatory evolution reveals functional interactions between ribosomal proteins S12, L14 and L19[J]. J Mol Biol, 2007, 366(1):207-215.
[42]	BARBOSA C, TREBOSC V, KEMMER C, et al. Alternative evolutionary paths to bacterial antibiotic resistance cause distinct collateral effects[J]. Mol Biol Evol, 2017, 34(9):2229-2244.
[43]	JONES D F. Proceedings of the sixth International congress of genetics[M]. New York:Brooklyn Botanic Garden, 1932.
[44]	MIRA P M, CRONA K, GREENE D, et al. Rational design of antibiotic treatment plans:a treatment strategy for managing evolution and reversing resistance[J]. PLoS One, 2015, 10(9):e0139387.
[45]	MALTAS J, WOOD K B. Pervasive and diverse collateral sensitivity profiles inform optimal strategies to limit antibiotic resistance[J]. PLoS Biol, 2019, 17(10):e3000515.
[46]	OZ T, GUVENEK A, YILDIZ S, et al. Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution[J]. Mol Biol Evol, 2014, 31(9):2387-2401.
[47]	BILGIN N, RICHTER A A, EHRENBERG M, et al. Ribosomal RNA and protein mutants resistant to spectinomycin[J]. EMBO J, 1990, 9(3):735-739.
[48]	BABA T, ARA T, HASEGAWA M, et al. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants:the Keio collection[J]. Mol Syst Biol, 2006, 2(1):2006. 0008.
[49]	LOZOVSKY E R, CHOOKAJORN T, BROWN K M, et al. Stepwise acquisition of pyrimethamine resistance in the malaria parasite[J]. Proc Natl Acad Sci U S A, 2009, 106(29):12025-12030.
[50]	LINDSEY H A, GALLIE J, TAYLOR S, et al. Evolutionary rescue from extinction is contingent on a lower rate of environmental change[J]. Nature, 2013, 494(7438):463-467.
[51]	REYNOLDS M G. Compensatory evolution in rifampin-resistant Escherichia coli[J]. Genetics, 2000, 156(4):1471-1481.
[52]	MACLEAN R C, PERRON G G, GARDNER A. Diminishing returns from beneficial mutations and pervasive epistasis shape the fitness landscape for rifampicin resistance in Pseudomonas aeruginosa[J]. Genetics, 2010, 186(4):1345-1354.
[53]	HALL A R, MACLEAN R C. Epistasis buffers the fitness effects of rifampicin- resistance mutations in Pseudomonas aeruginosa[J]. Evolution, 2011, 65(8):2370-2379.
[54]	SOLÉ M, FÀBREGA A, COBOS-TRIGUEROS N, et al. In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit:mechanisms of resistance and antimicrobial exposure[J]. J Antimicrob Chemother, 2015, 70(11):3004-3013.
[55]	DALLINGER W H. The president's address[J]. J Roy Microsc Soc, 1887, 7(2):185-199.
[56]	KLIRONOMOS J N, ALLEN M F, RILLIG M C, et al. Abrupt rise in atmospheric CO2 overestimates community response in a model plant-soil system[J]. Nature, 2005, 433(7026):621-624.
[57]	JAHN L J, MUNCK C, ELLABAAN M M H, et al. Adaptive laboratory evolution of antibiotic resistance using different selection regimes lead to similar phenotypes and genotypes[J]. Front Microbiol, 2017, 8:816.
[58]	LOSOS J B. Convergence, adaptation, and constraint[J]. Evolution, 2011, 65(7):1827-1840.
[59]	ROSENBERG E Y, BERTENTHAL D, NILLES M L, et al. Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein[J]. Mol Microbiol, 2003, 48(6):1609-1619.
[60]	LIN D L, TRAN T, ALAM J Y, et al. Inhibition of aminoglycoside 6'-N-acetyltransferase type Ib by zinc:reversal of amikacin resistance in Acinetobacter baumannii and Escherichia coli by a zinc ionophore[J]. Antimicrob Agents Chemother, 2014, 58(7):4238-4241.
[61]	RODRÍGUEZ-VERDUGO A, GAUT B S, TENAILLON O. Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress[J]. BMC Evol Biol, 2013, 13(1):50.
[62]	ALLEN R C, PFRUNDER-CARDOZO K R, HALL A R. Collateral sensitivity interactions between antibiotics depend on local abiotic conditions[J]. mSystems, 2021, 6(6):e01055-21.
[63]	PODNECKY N L, FREDHEIM E G A, KLOOS J, et al. Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli[J]. Nat Commun, 2018, 9(1):3673.