ライフサイエンスコーパス: multidrug resistance

1 pathway represents a linchpin in C. glabrata multidrug resistance.

2 valganciclovir, and a UL54 mutation confers multidrug resistance.

3 les in microbial pathogenesis, virulence and multidrug resistance.

4 ids as potential targets to fight pathogenic multidrug resistance.

5 ilome that were associated with plasmids and multidrug resistance.

6 ota makes it a potential reservoir of mobile multidrug resistance.

7 within phylogroup D-that is associated with multidrug resistance.

8 infections, with many strains demonstrating multidrug resistance.

9 association of baseline characteristics with multidrug resistance.

10 lthough all 3 epidemics were associated with multidrug resistance.

11 idence, and summarized clinical features and multidrug resistance.

12 idenced an ability to overcome cisplatin and multidrug resistance.

13 worldwide, with an increasing prevalence of multidrug resistance.

14 t is clinically important because it confers multidrug resistance.

15 explain natural cases of dyskinetoplasty and multidrug resistance.

16 rm the design of new strategies for tackling multidrug resistance.

17 seases and is associated with development of multidrug resistance.

18 protects us from toxic compounds and confers multidrug resistance.

19 protects us from toxic compounds and confers multidrug resistance.

20 terial pathogen increasingly associated with multidrug resistance.

21 ified harbinger mutations that often precede multidrug resistance.

22 hat is increasingly hard to treat because of multidrug resistance.

23 ay help to reduce the use of antibiotics and multidrug resistance.

24 when given with antiretroviral therapy, and multidrug resistance.

25 ntributors to the alarming rise in bacterial multidrug resistance.

26 linker instability, and a high incidence of multidrug resistance.

27 complexities in the mathematical modeling of multidrug resistance.

28 pecific therapeutics in the effort to combat multidrug resistance.

29 CAFO aerosols could serve as a reservoir of multidrug resistance.

30 nfections that are difficult to treat due to multidrug resistance.

31 path leading to the emergence of high-level, multidrug resistance.

32 of tuberculosis incidence and prevalence of multidrug resistance.

33 ost critical mechanisms leading to bacterial multidrug resistance.

34 s, which may have important implications for multidrug resistance.

35 ibiotics for tackling the issue of bacterial multidrug resistance.

36 etics and contributing to the development of multidrug resistance.

37 re mediated by increased copy numbers of the multidrug resistance 1 gene (pvmdr1) may select for mefl

38 und to be a poor substrate (>30 muM) for the multidrug resistance 1 protein, suggesting low likelihoo

39 c-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids

40 -23 and IL-17 was effectively modeled in the multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse mode

41 Deficiency of multidrug resistance 2 (mdr2), a canalicular phospholipi

42 Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mi

43 Treatment of multidrug resistance 2 gene knockout (Mdr2(-/-) ) mice w

44 We have shown that partial hepatectomy in multidrug resistance 2 knockout (Mdr2(-/-) ) mice, a mod

45 Wild-type and multidrug resistance 2 knockout mice (9-11 weeks) were t

46 rosis, histamine secretion, and bile flow in multidrug resistance 2 knockout mice.

47 antly reduces FBP levels in HCC cells and in multidrug resistance 2-deficient mice that develop HCC d

48 Defects in multidrug resistance 3 gene (MDR3), which encodes the ca

49 The recent increase in multidrug resistance against bacterial infections has be

50 espite the complex evolutionary landscape of multidrug resistance, alternating-drug therapy can slow

51 Increasing multidrug resistance among ExPEC strains constitutes a m

52 inical success, followed by echinocandin and multidrug resistance among some Candida species, especia

53 st that the HpnN transporter is critical for multidrug resistance and cell wall remodeling in Burkhol

54 1 inhibitors, leading to further research on multidrug resistance and combination chemotherapy.

55 verexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by

56 , respectively, and 18.3% displayed combined multidrug resistance and DCS; rates of azithromycin and

57 Among Salmonella Typhi, rates of multidrug resistance and decreased ciprofloxacin suscept

58 se findings therefore identify a new axis in multidrug resistance and highlight a radical new functio

59 Emerging threats, including multidrug resistance and increasing urbanization in regi

60 binding cassette (ABCC) transporters mediate multidrug resistance and ion conductance regulation.

61 ia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydro

62 belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage re

63 mps like P-glycoprotein (P-gp, ABCB1) confer multidrug resistance and mutant ABC proteins are respons

64 ncrease in the number of plasmids conferring multidrug resistance and strain replacement by a resista

65 lic health problem owing to the emergence of multidrug resistance and the lack of broadly efficient v

66 Multidrug resistances and the failure of chemotherapies

67 % of Salmonella Typhimurium isolates) showed multidrug resistance, and <2.5% showed DCS.

68 ed stemness to nonstem cancer cells, induced multidrug resistance, and enhanced the migration potenti

69 resistance, second-line injectable-resistant multidrug resistance, and extensive multidrug resistance

70 ppropriate antibacterial use contributing to multidrug resistance, and increased morbidity and mortal

71 Hypervirulence, multidrug resistance, and opportunism have been proposed

72 ination therapy with a potential to overcome multidrug resistance, and real-time readout on the treat

73 These nanocomplexes, which target multidrug resistance, are not only able to bypass the P-

74 Multidrug resistance arising from the activity of integr

75 Overexpression of plasma membrane multidrug resistance-associated protein 1 (MRP-1) in Ewi

76 Multidrug resistance-associated protein 1 (MRP1) is a dr

77 cytometry and immunostaining have shown that multidrug resistance-associated protein 1 (MRP1) is prev

78 P-Glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1),

79 th respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1).

80 sporters, bile salt export pump (Abcb11) and multidrug resistance-associated protein 2 (Abcc2).

81 ane cholesterol on the transport kinetics of multidrug resistance-associated protein 2 (MRP2) and of

82 holate cotransporting polypeptide (NTCP) and multidrug resistance-associated protein 2 (MRP2) by conv

83 eval of the bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) from th

84 Previous studies suggest that the multidrug resistance-associated protein 2 (Mrp2) transpo

85 1A1 (Oatp1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 (Mrp2), and th

86 0 administration significantly induced renal multidrug resistance-associated protein 2 and 4, peroxis

87 Multidrug resistance-associated protein-1 (MRP-1), an ac

88 dramatic UL138-mediated loss of cell surface multidrug resistance-associated protein-1 (MRP1) and the

89 ycoprotein, ATP binding cassette b1 (Abcb1); multidrug resistance-associated protein-2 (Mrp2), Abcc2;

90 , multidrug-resistance protein 1 (MDR1), and multidrug-resistance-associated protein (MRP) 2 and 3 el

91 Inhibitors of TDF's apical multidrug-resistance-associated protein efflux-transport

92 In addition, tumors often develop multidrug resistance based on the cellular efflux of che

93 verage can greatly speed up the evolution of multidrug resistance by allowing mutations to accumulate

94 erfamily make a considerable contribution to multidrug resistance by catalysing efflux of myriad stru

95 extrusion (MATE) transporters contribute to multidrug resistance by extruding different drugs across

96 Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics

97 pound extrusion (MATE) transporters underpin multidrug resistance by using the H(+) or Na(+) electroc

98 il, indicating that the protein behaves as a multidrug resistance carrier.

99 portant being severe side effects along with multidrug resistance developed against them.

100 EmrE is a multidrug resistance efflux pump with specificity to a w

101 sed on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is

102 antifungal stewardship is critical to limit multidrug resistance emergence.

103 earch demonstrates that TCC can select for a multidrug resistance encoding gene in mixed community an

104 The multidrug resistance-encoding IncA/C conjugative plasmid

105 Variants of the multidrug resistance gene (MDR1/ABCB1) have been associa

106 Herein, using the mouse model of PSC (multidrug resistance gene 2 knockout), the hepatic knock

107 in administration on hepatic fibrosis in the multidrug resistance gene 2-knockout (Mdr2(-/-)) mouse m

108 e-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasit

109 Additionally, putative multidrug resistance genes (emrE) were found in YSLPV1 a

110 tetracycline resistance genes (manures) and multidrug resistance genes (greenhouse soils).

111 Quantification of several key multidrug resistance genes showed a much higher number o

112 on of ssa and transposable elements encoding multidrug resistance genes triggered the expansion of sc

113 of resistance to single drug classes and now multidrug resistance greatly hampers patient management.

114 cells endowed with tumorigenic potential and multidrug resistance has been isolated from different tu

115 Multidrug resistance has emerged in all 3 serovars and i

116 e infections worldwide, is rapidly acquiring multidrug resistance, hastening the need for selective n

117 Of predefined risk factors for multidrug resistance (hereafter, risk factors), the most

118 Recent emergence of multidrug resistance highlights the need to develop nove

119 We found multidrug resistance in 33 (9%) of 361 patients.

120 tance of PXR as a drug target for countering multidrug resistance in anticancer treatments.

121 lications for understanding the emergence of multidrug resistance in bacteria.

122 These proteins contribute to multidrug resistance in both mammalian and bacterial cel

123 red a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumou

124 rfamily due to its involvement in developing multidrug resistance in cancer cells.

125 nsport protein is a major target to overcome multidrug resistance in cancer patients.

126 s key position, ABC transporters can mediate multidrug resistance in cancer therapy and their dysfunc

127 specific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles

128 eutics, could therefore be used to attenuate multidrug resistance in cancers.

129 Transcription factors MarR and MarA confer multidrug resistance in enteric bacteria by modulating e

130 , such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria.

131 viral replicative fitness is a mechanism of multidrug resistance in HCV.

132 he best-known mediators of drug efflux-based multidrug resistance in many cancers.

133 idrug resistance-related protein 1-dependent multidrug resistance in patterned adenocarcinoma cervica

134 There is evidence of multidrug resistance in salmonellae that warrants vigila

135 g efflux pump MepA is a major contributor to multidrug resistance in Staphylococcus aureus.

136 BCC1 was originally discovered as a cause of multidrug resistance in tumor cells.

137 Firmicutes multidrug resistance inc18 plasmids encode parS sites an

138 Multidrug resistance, including to ceftriaxone, will pos

139 Here, a new form of multidrug resistance, inducible drug glucuronidation, is

140 ecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1.

141 fferent cancer treatments with synergism and multidrug resistance inhibition, which has great potenti

142 Pan- or multidrug resistance is a central problem in clinical on

143 Multidrug resistance is a global threat as the clinicall

144 herapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility

145 Multidrug resistance is a major barrier against successf

146 We propose that multidrug resistance is a multifactorial process and tha

147 Bacterial multidrug resistance is a significant health issue.

148 Multidrug resistance is common, and resistance to third-

149 Rapid and accurate detection of multidrug resistance is essential for effective treatmen

150 gut microbiota, its role as a reservoir for multidrug resistance is not well understood.

151 Although multidrug resistance is uncommon, increasing reports of

152 Multidrug-resistance is a substantial threat to global e

153 by entecavir and tenofovir even in cases of multidrug resistance, leading to decreased rates of hepa

154 their parent compounds (e.g., circumventing multidrug resistance), making the dimerization concept h

155 replicative fitness can be a determinant of multidrug resistance may explain why the virus is less s

156 Cancer cells can develop multidrug resistance (MDR) after prolonged exposure to c

157 bacterial resistance in hospitals, including multidrug resistance (MDR) and its association with seri

158 Multidrug resistance (MDR) attenuates the chemotherapy e

159 Multidrug resistance (MDR) in cancer cells is a substant

160 e amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a

161 RP1), which are involved in the formation of multidrug resistance (MDR) in cancer chemotherapy.

162 expression of P-glycoprotein (Pgp) increases multidrug resistance (MDR) in cancer, which greatly impe

163 , which has been suggested to be involved in multidrug resistance (MDR) in cancer.

164 of recent transmission to the high rates of multidrug resistance (MDR) in this area, Mycobacterium t

165 Multidrug resistance (MDR) is a major cause of failure i

166 Multidrug resistance (MDR) is a major challenge for canc

167 Multidrug resistance (MDR) is a major impediment to canc

168 Multidrug resistance (MDR) is a major obstacle in cancer

169 Multidrug resistance (MDR) is a major obstacle to the su

170 Multidrug resistance (MDR) is a significant problem in t

171 f the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug

172 This so-called multidrug resistance (MDR) may be reversed by selective,

173 Multidrug resistance (MDR) mediated by ATP-binding casse

174 Multidrug resistance (MDR) mediated by P-glycoprotein (P

175 Among the mechanisms of treatment failure is multidrug resistance (MDR) mediated by the ABCB1, ABCC1,

176 However, multidrug resistance (MDR) of cancer cells has remained

177 , which makes it a major player in mediating multidrug resistance (MDR) of cancer cells.

178 The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such wh

179 The circumvention of multidrug resistance (MDR) plays a critically important

180 However, multidrug resistance (MDR) remains a major obstacle to e

181 ay of treatment; however, the development of multidrug resistance (MDR) restricts the efficacy of cur

182 lococcus aureus (MRSA) infection was 24% and multidrug resistance (MDR) was observed in 87% of the is

183 ) plays a crucial role in the development of multidrug resistance (MDR), a major obstacle for success

184 Conversely it is one of the main causes of multidrug resistance (MDR), being capable of effluxing m

185 d monoresistance, rifampicin monoresistance, multidrug resistance (MDR), fluoroquinolone-resistant mu

186 pe characterized by increased proliferation, multidrug resistance (MDR), invasion and metastasis.

187 tivity relationships essential in overcoming multidrug resistance (MDR), some correlations between MD

188 molecule chemosensitizers can reverse cancer multidrug resistance (MDR), thus significantly improving

189 f RND-type efflux pumps is a major factor in multidrug resistance (MDR), which makes these pumps impo

190 Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two indep

191 Furthermore, the cytotoxicity and multidrug resistance (MDR)-reversal ability of selected

192 s out of the bacterium, conferring intrinsic multidrug resistance (MDR).

193 cer agents, leading to the phenomenon called multidrug resistance (MDR).

194 ins palliative because of the development of multidrug resistance (MDR).

195 ic metabolism, including a decrease in ABCB1/multidrug resistance (MDR)1 p-glycoprotein (p-gp) expres

196 Increased prevalence of multidrug resistance (MDR; 94% compared to 60% in layers

197 induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5.

198 site gene mutations, increased production of multidrug-resistance (MDR) efflux pumps, modifying enzym

199 Hence the TipA multidrug resistance mechanism is directed against the s

200 In addition, other molecules targeting multidrug-resistance mechanisms, such as efflux pumps, a

201 ce, we provide a framework for understanding multidrug resistance, mediated by analogous systems, acr

202 demic C difficile ribotypes characterised by multidrug resistance might depend on antibiotic selectio

203 fepime, resistance to meropenem, presence of multidrug resistance, nonabdominal surgery, and prior an

204 protein (Pgp) is an efflux pump important in multidrug resistance of cancer cells and in determining

205 and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, as w

206 established mutations could confer potential multidrug resistance on pH1N1 or HPAI H5N1 viruses.

207 ted with HIV-infected patients (P = .03) and multidrug resistance (OR, 6.6; 95% CI, 2.5-17.2; P < .00

208 morphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, int

209 orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae

210 Given the observed multidrug resistance patterns and the possibility of tra

211 s hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype.

212 a novel prophage repertoire, and an expanded multidrug resistance plasmid.

213 This updated model of the multidrug resistance problem integrates both genetic and

214 The efflux of antimony through multidrug resistance protein (MDR)-1 is the key factor i

215 ociated proteins caveolin-1, syntaxin-6, and multidrug resistance protein 1 (MDR1) in brain endotheli

216 Multidrug resistance protein 1 (MRP1) actively transport

217 histochemical expression of bronchopulmonary multidrug resistance protein 1 (MRP1) and permeability g

218 The multidrug resistance protein 1 (MRP1) encoded by ABCC1 w

219 eans to overcome resistance by silencing the multidrug resistance protein 1 (MRP1), before chemothera

220 ned against P-glycoprotein (P-gp, ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) to confirm

221 The ATP-binding cassette (ABC) transporter multidrug resistance protein 1 (MRP1/ABCC1) is responsib

222 iron release from cells via the transporter multidrug resistance protein 1 (MRP1/ABCC1).

223 s classified as ABCC2 or Leishmania donovani multidrug resistance protein 2 (LdMRP2).

224 transport protein 1a and 1b (Oatp1a/1b) and multidrug resistance protein 2 (Mrp2) was investigated b

225 vity of two other major efflux transporters, multidrug resistance protein 2 and breast cancer resista

226 apical membrane to subapical puncta, whereas multidrug resistance protein 2 distributions were not ch

227 10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine res

228 information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its rol

229 ansporters, bile salt export pump (BSEP) and multidrug resistance protein 3 (MDR3).

230 The human multidrug resistance protein 3 (MDR3/ABCB4) belongs to t

231 hydroxysteroid sulfotransferase enzyme 2A1, multidrug resistance protein 3, and apical sodium-depend

232 drugs are either substrates or inhibitors of multidrug resistance protein 4 (MRP4), such as the anti-

233 In this study, we used multidrug resistance protein 4 (MRP4)-expressing cell li

234 In this study, we evaluated the role of multidrug resistance protein 4 (MRP4, or ABCC4), a nucle

235 signaling cascade (phospholipase A2, COX-2, multidrug resistance protein 4, and G-protein-coupled pr

236 We hypothesized that multidrug resistance protein 4/ATP binding cassette tran

237 Pase beta (flippase), the hematopoietic cell multidrug resistance protein ABC transporter (floppase),

238 tivation of TGFbeta, and upregulation of the multidrug resistance protein ABCG2.

239 The multidrug resistance protein MRP1 is an ATP-binding cass

240 The multidrug resistance protein MRP1 is an ATP-driven pump

241 rough adherens junction, tight junction, and multidrug resistance protein regulation.

242 ng cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp).

243 thiol/disulfide balance, greater extents of multidrug resistance protein-1 (MRP1) expression, and gr

244 ers breast cancer resistance protein (BCRP), multidrug-resistance protein 1 (MDR1), and multidrug-res

245 ferase and the biliary phospholipid floppase multidrug-resistance protein 2 (Mdr2/Abcb4), resulting i

246 sporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-g

247 subfamily includes pumps, the long and short multidrug resistance proteins (MRPs), and an ATP-gated a

248 One family of these pumps, the small multidrug resistance proteins (SMRs), consists of protei

249 ucture of heterodimeric Thermus thermophilus multidrug resistance proteins A and B (TmrAB), which not

250 on antiparallel homo- or heterodimeric small multidrug resistance proteins and examine whether the in

251 n-regulation of miRNA downstream targets and multidrug resistance proteins and extent of apoptosis we

252 sment of the affinity of drug candidates for multidrug resistance proteins is central to predict in v

253 the expression of anti-apoptotic factors and multidrug resistance proteins.

254 With the rise of multidrug resistance, Pseudomonas aeruginosa infections

255 upregulation of a single gene, encoding the multidrug resistance pump ABCB1.

256 vity of the transcription factor Lactococcal multidrug resistance Regulator (LmrR) as a generic bindi

257 ) can quantitatively and noninvasively track multidrug resistance-related protein 1-dependent multidr

258 a therapeutic target for the development of multidrug resistance reversal agents.

259 cobacteria, thus turning out to be promising multidrug-resistance-reversing agents.

260 to the case detection group (n=1439) and the multidrug-resistance risk group (n=314).

261 tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosi

262 in all analyses, whereas participants in the multidrug-resistance risk group were only included in an

263 To cope with the global bacterial multidrug resistance, scientific communities have devote

264 resistance (MDR), fluoroquinolone-resistant multidrug resistance, second-line injectable-resistant m

265 transport proteins are members of the small multidrug resistance (SMR) family that are composed of f

266 Our results support sepsis severity, but not multidrug-resistance status as being an important predic

267 Multidrug-resistance status did not result in excess mor

268 Clinical outcomes were compared according to multidrug-resistance status, sepsis classification, demo

269 It constitutes a minimal autoregulated multidrug resistance system against numerous thiopeptide

270 cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells

271 The emergence of bacterial multidrug resistance to antibiotics threatens to cause r

272 Multidrug resistance to at least 3 additional antibiotic

273 operties of these two important molecules in multidrug resistance to chemotherapy.

274 Multidrug resistance to current Food and Drug Administra

275 e transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are ess

276 Upregulating Mcl-1 introduces multidrug resistance to standard therapies, whereas its

277 esistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and p

278 reened a known mutation(s) that could confer multidrug resistance to the currently approved NAIs osel

279 loroquine resistance transporter (PfCRT) and multidrug resistance transporter (PfMDR1) can modulate t

280 Multidrug resistance transporter 3/ATP-binding cassette

281 EmrE is a small multidrug resistance transporter found in Escherichia co

282 de that resembles that of Cam binding to the multidrug resistance transporter MdfA.

283 r in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitato

284 and was a highly sensitive substrate of the multidrug resistance transporter P-glycoprotein (P-gp).

285 EmrE is a small multidrug resistance transporter that has been well stud

286 EmrE, a small multidrug resistance transporter, serves as an ideal mod

287 ctionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter.

288 Multidrug resistance was defined as resistance to 3 or m

289 Multidrug resistance was detected among MRSA from all so

290 progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification o

291 Multidrug resistance was found in 4% (9/203) of the isol

292 eptible to most antibiotics, indicating that multidrug resistance was not the dominant reason for pre

293 Multidrug resistance was present in 23.9% (84/351) of NT

294 We found that multidrug resistance was strongly associated with an EMT

295 1 integrons, which has been associated with multidrug resistance, was detected in CAFOs but not in h

296 micking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle

297 n very young children and the development of multidrug resistance, which threatens efficacy of antimi

298 K-Fmoc-VE2 may have the potential to reverse multidrug resistance, which was supported by its inhibit

299 esistant multidrug resistance, and extensive multidrug resistance with resistance to both a fluoroqui

300 ed, the amino acid substitutions that confer multidrug resistance with undiminished viral fitness rem