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Aaron C. Crawford, Laura E. Lehtovirta-Morley, Omran Alamir, Maria J. Niemiec, Bader Alawfi, Mohammad Alsarraf, Volha Skrahina, Anna C. B. P. Costa, Andrew Anderson, Sujan Yellagunda, Elizabeth R. Ballou, Bernhard Hube, Constantin F. Urban, Duncan Wilson
Biphasic zinc compartmentalisation in a human fungal pathogen
www.plospathogens.org
www.plospathogens.org
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(transporters)Tj
5.0853 0 Td
(have)Tj
2.058 0 Td
(now)Tj
1.9615 0 Td
(been)Tj
2.1203 0 Td
(characterised)Tj
5.5049 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(major)Tj
-33.681 -1.2983 Td
(human)Tj
3.0784 0 Td
(fungal)Tj
2.7269 0 Td
(pathogens)Tj
/F12 1 Tf
4.3029 0 Td
[()10()10()4()2()6()-8()4()4()12()-4()]TJ
4.4391 0 Td
[()-8()12( )18()10()2()22()7()-4()]TJ
/F8 1 Tf
(,)Tj
/F12 1 Tf
4.3426 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.1792 0 Td
[()7()12()7()10()4()4()22()7()12( )]TJ
/F8 1 Tf
(,)Tj
/F12 1 Tf
4.9663 0 Td
[()13()-20(\n)-13()12()11()4()7()4()7()1()-4()]TJ
5.3121 0 Td
[()6()7()11()9()11()-9( )6()16()]TJ
/F8 1 Tf
4.8188 0 Td
(and)Tj
/F12 1 Tf
-35.1663 -1.2983 Td
[()]TJ
1.0658 0 Td
[()2()22()7()12()]TJ
/F8 1 Tf
2.2507 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(17)Tj
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(],)Tj
3.5432 0 Td
(and)Tj
1.7292 0 Td
(Zip)Tj
1.61 0 Td
(transporter)Tj
4.7169 0 Td
(mutants)Tj
3.5092 0 Td
(for)Tj
1.389 0 Td
(all)Tj
1.1452 0 Td
(four)Tj
1.9162 0 Td
(species)Tj
2.9934 0 Td
(exhibit)Tj
2.9763 0 Td
(attenuated)Tj
4.4334 0 Td
(virulence,)Tj
-33.2785 -1.3039 Td
(underscoring)Tj
5.5615 0 Td
(the)Tj
1.4683 0 Td
(importance)Tj
4.8302 0 Td
(of)Tj
1.0148 0 Td
(zinc)Tj
1.8709 0 Td
(uptake)Tj
2.9197 0 Td
(for)Tj
1.3889 0 Td
(fungal,)Tj
2.9537 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(bacterial)Tj
3.6227 0 Td
(pathogenicity.)Tj
/F12 1 Tf
-28.2839 -1.2982 Td
[()-2()16()6()12()4()4()]TJ
3.6056 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.3959 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(normal)Tj
3.1465 0 Td
(commensal)Tj
4.8018 0 Td
(member)Tj
3.5887 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
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(human)Tj
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(gastrointestinal)Tj
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(microbiota)Tj
-33.1481 -1.2983 Td
(and)Tj
1.7291 0 Td
(other)Tj
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(mucosal)Tj
3.5377 0 Td
(surfaces,)Tj
3.6396 0 Td
(a)Tj
0.652 0 Td
(common)Tj
3.8437 0 Td
(cause)Tj
2.3925 0 Td
(of)Tj
1.0148 0 Td
(mucosal)Tj
3.5376 0 Td
(infections,)Tj
4.3766 0 Td
(and)Tj
1.7292 0 Td
(a)Tj
0.6576 0 Td
(serious)Tj
3.0387 0 Td
(invasive)Tj
-32.4961 -1.3039 Td
(pathogen)Tj
3.9401 0 Td
(in)Tj
1.0375 0 Td
(certain)Tj
2.982 0 Td
(patient)Tj
3.0104 0 Td
(groups)Tj
2.9706 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
2.075 0 Td
(In)Tj
1.1112 0 Td
(fact,)Tj
1.8878 0 Td
(invasive)Tj
3.4299 0 Td
(candidiasis,)Tj
4.8643 0 Td
(predominantly)Tj
6.1851 0 Td
(caused)Tj
-33.4939 -1.2983 Td
(by)Tj
/F12 1 Tf
1.1792 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
(,)Tj
3.6283 0 Td
(affects)Tj
2.7326 0 Td
(more)Tj
2.3414 0 Td
(than)Tj
2.0296 0 Td
(a)Tj
0.6576 0 Td
(quarter)Tj
3.1521 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(million)Tj
3.1237 0 Td
(individuals)Tj
4.6488 0 Td
(each)Tj
2.0296 0 Td
(year)Tj
1.8992 0 Td
(and)Tj
1.7348 0 Td
(is)Tj
0.8447 0 Td
(responsible)Tj
-32.7342 -1.2982 Td
(for)Tj
1.3832 0 Td
(at)Tj
0.9525 0 Td
(least)Tj
1.9842 0 Td
(50,000)Tj
2.8233 0 Td
(deaths)Tj
2.795 0 Td
(annually)Tj
3.6566 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
2.0806 0 Td
(We)Tj
1.6044 0 Td
(have)Tj
2.0637 0 Td
(previously)Tj
4.3483 0 Td
(shown)Tj
2.8516 0 Td
(that)Tj
1.7745 0 Td
(this)Tj
1.6781 0 Td
(fungus)Tj
2.9367 0 Td
(can)Tj
1.627 0 Td
(scav-)Tj
-34.5597 -1.2983 Td
(enge)Tj
2.0806 0 Td
(zinc)Tj
1.8708 0 Td
(via)Tj
1.3777 0 Td
(the)Tj
1.4683 0 Td
(secreted)Tj
3.4696 0 Td
(protein)Tj
3.1577 0 Td
(Pra1)Tj
2.058 0 Td
(and)Tj
1.7291 0 Td
(that)Tj
1.7802 0 Td
(this)Tj
1.6724 0 Td
(zincophore)Tj
5.5105 0 Td
(system)Tj
2.9367 0 Td
(is)Tj
0.8504 0 Td
(important)Tj
4.2803 0 Td
(for)Tj
-34.2423 -1.3039 Td
(host)Tj
1.9048 0 Td
(cell)Tj
1.5477 0 Td
(damage)Tj
3.3165 0 Td
(in)Tj
1.0262 0 Td
(tissue)Tj
2.4548 0 Td
(culture)Tj
3.0273 0 Td
(infection)Tj
3.7814 0 Td
(models)Tj
3.0955 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.0692 0 Td
(However,)Tj
4.0706 0 Td
(a)Tj
/F12 1 Tf
0.6463 0 Td
[()11()20()]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
2.5851 0 Td
(mutant)Tj
3.1408 0 Td
(is)Tj
0.8391 0 Td
(hyper-vir-)Tj
-33.5053 -1.2983 Td
(ulent)Tj
2.262 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(mouse)Tj
2.8573 0 Td
(model)Tj
2.7496 0 Td
(of)Tj
1.0148 0 Td
(infection)Tj
3.7871 0 Td
(as)Tj
1.0148 0 Td
(it)Tj
0.788 0 Td
(also)Tj
1.7688 0 Td
(serves)Tj
2.6135 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(ligand)Tj
2.7099 0 Td
(for)Tj
1.389 0 Td
(neutrophil)Tj
4.4503 0 Td
(alphaMbeta2)Tj
-30.7613 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(].)Tj
1.1962 -1.3039 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(study)Tj
2.3924 0 Td
(we)Tj
1.3266 0 Td
(have)Tj
2.0579 0 Td
(functionally)Tj
5.0117 0 Td
(dissected)Tj
3.8324 0 Td
(zinc)Tj
1.8708 0 Td
(transport)Tj
3.9288 0 Td
(in)Tj
/F12 1 Tf
1.0375 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
(.)Tj
3.6227 0 Td
(We)Tj
1.61 0 Td
(identified)Tj
4.0592 0 Td
(nine)Tj
-35.7956 -1.2982 Td
(putative)Tj
3.4412 0 Td
(zinc)Tj
1.8708 0 Td
(transporters)Tj
5.0854 0 Td
(including)Tj
4.0421 0 Td
(two)Tj
1.7065 0 Td
(predicted)Tj
4.0025 0 Td
(plasma)Tj
3.0274 0 Td
(membrane)Tj
4.5694 0 Td
(Zip)Tj
1.6044 0 Td
(proteins,)Tj
3.7417 0 Td
(Zrt1)Tj
1.9672 0 Td
(and)Tj
-35.0586 -1.2983 Td
(Zrt2,)Tj
2.1883 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(five)Tj
1.6554 0 Td
(ZnT)Tj
1.9786 0 Td
(proteins.)Tj
3.7417 0 Td
(Regulatory)Tj
4.5694 0 Td
(and)Tj
1.7292 0 Td
(functional)Tj
4.3086 0 Td
(analysis)Tj
3.3278 0 Td
(demonstrates)Tj
5.5956 0 Td
(that)Tj
1.7745 0 Td
(pH-)Tj
-34.7185 -1.3039 Td
(dependent)Tj
4.456 0 Td
(adaptation)Tj
4.49 0 Td
(to)Tj
1.0205 0 Td
(zinc)Tj
1.8765 0 Td
(limitation)Tj
4.1726 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(conserved)Tj
4.2576 0 Td
(in)Tj
1.0375 0 Td
(fungi,)Tj
2.5455 0 Td
(but)Tj
1.5477 0 Td
(that)Tj
1.7801 0 Td
(distinct)Tj
3.2145 0 Td
(trans-)Tj
-33.4769 -1.2983 Td
(porter)Tj
2.7099 0 Td
(subclasses)Tj
4.2235 0 Td
(differentially)Tj
5.3065 0 Td
(contribute)Tj
4.388 0 Td
(to)Tj
1.0261 0 Td
(growth)Tj
/F12 1 Tf
3.0727 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3()]TJ
/F8 1 Tf
1.8199 0 Td
(for)Tj
1.3889 0 Td
(different)Tj
3.6567 0 Td
(human)Tj
3.0784 0 Td
(pathogenic)Tj
-31.6854 -1.2983 Td
(species.)Tj
3.2201 0 Td
(Moreover,)Tj
4.3993 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.4684 0 Td
(first)Tj
1.8085 0 Td
(time,)Tj
2.2507 0 Td
(we)Tj
1.3322 0 Td
(define)Tj
2.6986 0 Td
(a)Tj
0.652 0 Td
(molecular)Tj
4.2179 0 Td
(mechanism)Tj
4.8472 0 Td
(of)Tj
1.0148 0 Td
(zincosomal)Tj
4.7452 0 Td
(zinc)Tj
-34.0382 -1.2982 Td
(accumulation)Tj
5.6749 0 Td
(in)Tj
1.0374 0 Td
(a)Tj
0.652 0 Td
(human)Tj
3.0784 0 Td
(fungal)Tj
2.7326 0 Td
(pathogen.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 325.9842 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
3.7984 0 Td
(and)Tj
1.989 0 Td
(discussion)Tj
/F14 1 Tf
-5.7874 -1.4976 Td
(Identification)Tj
5.9669 0 Td
(of)Tj
1.0678 0 Td
(zinc)Tj
1.937 0 Td
(importers)Tj
4.3748 0 Td
(in)Tj
/F15 1 Tf
1.063 0 Td
[()-3()12()5()5()-1()-1()]TJ
3.7559 0 Td
[()9()12()4()-1()3()12()-10( )]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Zinc)Tj
2.0579 0 Td
(transport)Tj
3.9288 0 Td
(in)Tj
1.0375 0 Td
(eukaryotes)Tj
4.5127 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1508 0 Td
(mediated)Tj
3.9402 0 Td
(by)Tj
1.1848 0 Td
(members)Tj
3.9458 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(Zip)Tj
1.6044 0 Td
(and)Tj
1.7291 0 Td
(ZnT)Tj
1.9842 0 Td
(protein)Tj
3.1521 0 Td
(fami-)Tj
-34.3386 -1.2982 Td
(lies,)Tj
1.7404 0 Td
(which)Tj
2.6532 0 Td
(transport)Tj
3.9231 0 Td
(their)Tj
2.109 0 Td
(substrate)Tj
3.8041 0 Td
(to)Tj
1.0261 0 Td
(or)Tj
1.0942 0 Td
(from)Tj
2.211 0 Td
(the)Tj
1.4683 0 Td
(cytoplasm,)Tj
4.5071 0 Td
(respectively)Tj
4.8812 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.6044 0 Td
(In)Tj
1.1055 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
-34.5484 -1.3039 Td
(determine)Tj
4.3199 0 Td
(how)Tj
/F12 1 Tf
1.9389 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0715 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.3959 0 Td
(acquires)Tj
3.5376 0 Td
(zinc)Tj
1.8709 0 Td
(from)Tj
2.2053 0 Td
(its)Tj
1.1452 0 Td
(environment,)Tj
5.6579 0 Td
(we)Tj
1.3266 0 Td
(first)Tj
1.8085 0 Td
(focussed)Tj
3.6397 0 Td
(on)Tj
1.2755 0 Td
(Zip)Tj
1.6044 0 Td
(trans-)Tj
-34.7978 -1.2983 Td
(porters.)Tj
3.2938 0 Td
(Using)Tj
2.5965 0 Td
(the)Tj
1.474 0 Td
(FungiDB)Tj
3.8721 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(])Tj
1.8482 0 Td
(InterPro)Tj
3.6397 0 Td
(domain-finder)Tj
6.1001 0 Td
(\(PFAM:)Tj
3.4525 0 Td
(PF02535;)Tj
0.83 0.64 0.02 0 k
3.9062 0 Td
(http://fungidb.)Tj
-30.1831 -1.2983 Td
(org/fungidb/)Tj
0 g
(\))Tj
5.6919 0 Td
(we)Tj
1.3266 0 Td
(identified)Tj
4.0592 0 Td
(four)Tj
1.9162 0 Td
(Zip-type)Tj
/F12 1 Tf
3.651 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.3959 0 Td
(proteins.)Tj
3.7417 0 Td
(Only)Tj
2.2167 0 Td
(Zrt1)Tj
1.9672 0 Td
(and)Tj
1.7291 0 Td
(Zrt2)Tj
1.9673 0 Td
(are)Tj
1.4456 0 Td
(pre-)Tj
-34.1742 -1.3039 Td
(dicted)Tj
2.6872 0 Td
(plasma)Tj
3.033 0 Td
(membrane)Tj
4.5638 0 Td
(transporters.)Tj
5.3121 0 Td
(In)Tj
1.1055 0 Td
(contrast,)Tj
3.6907 0 Td
(Zrt3)Tj
1.9615 0 Td
(and)Tj
1.7348 0 Td
(orf19.5428)Tj
4.4617 0 Td
(share)Tj
2.3414 0 Td
(similarity)Tj
4.0025 0 Td
(with)Tj
/F12 1 Tf
-34.8942 -1.2982 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
0.9014 0 Td
[()7()2()20()-5()-13()-4()10()4()6()]TJ
/F8 1 Tf
3.9117 0 Td
(Zrt3)Tj
1.9673 0 Td
(\(vacuolar)Tj
3.9571 0 Td
(zinc\))Tj
2.211 0 Td
(and)Tj
1.7292 0 Td
(Atx2)Tj
2.1429 0 Td
(\(Golgi)Tj
2.761 0 Td
(manganese\))Tj
5.0173 0 Td
(transporters.)Tj
5.312 0 Td
(We)Tj
1.6101 0 Td
(had)Tj
1.7065 0 Td
(previously)Tj
-33.2275 -1.2983 Td
(generated)Tj
4.1328 0 Td
(a)Tj
/F12 1 Tf
0.6577 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
3.3959 0 Td
[()-19()]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
2.3527 0 Td
(mutant)Tj
3.1465 0 Td
(as)Tj
1.0147 0 Td
(part)Tj
1.8369 0 Td
(of)Tj
1.0148 0 Td
(our)Tj
1.6271 0 Td
(efforts)Tj
2.7552 0 Td
(to)Tj
1.0262 0 Td
(characterise)Tj
4.9832 0 Td
(the)Tj
1.4684 0 Td
(fungal)Tj
2.7269 0 Td
(zinco-)Tj
-33.2048 -1.3039 Td
(phore,)Tj
2.7892 0 Td
(Pra1)Tj
2.0636 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.075 0 Td
(In)Tj
1.1112 0 Td
(this)Tj
1.6724 0 Td
(previous)Tj
3.651 0 Td
(study)Tj
2.3867 0 Td
(we)Tj
1.3266 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7802 0 Td
(Zrt1)Tj
1.9672 0 Td
(was)Tj
1.6951 0 Td
(essential)Tj
3.583 0 Td
(for)Tj
1.389 0 Td
(the)Tj
1.4683 0 Td
(reassociation)Tj
-31.5777 -1.2983 Td
(of)Tj
1.0147 0 Td
(soluble)Tj
3.0388 0 Td
(Pra1)Tj
2.0579 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(fungal)Tj
2.7326 0 Td
(cell)Tj
1.559 0 Td
(surface,)Tj
3.2712 0 Td
(indicating)Tj
4.2689 0 Td
(that)Tj
1.7802 0 Td
(Zrt1)Tj
1.9615 0 Td
(is)Tj
0.8504 0 Td
(likely)Tj
2.3528 0 Td
(cell)Tj
1.559 0 Td
(surface-localised.)Tj
/F12 1 Tf
-28.9415 -1.2983 Td
[()47( )]TJ
/F8 1 Tf
(,)Tj
2.6702 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(other)Tj
2.3471 0 Td
(hand,)Tj
2.4831 0 Td
(was)Tj
1.7008 0 Td
(\(at)Tj
1.2926 0 Td
(time)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(writing\))Tj
3.4582 0 Td
(annotated)Tj
4.2406 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
/F12 1 Tf
1.4683 0 Td
[()-2()16()6()12()4()4()]TJ
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(\).)Tj
1.9899 0 Td
(Similar)Tj
3.1011 0 Td
(pH)Tj
1.5023 0 Td
(dependent)Tj
4.4617 0 Td
(growth)Tj
3.0727 0 Td
(patterns)Tj
-34.2989 -1.2983 Td
(and)Tj
1.7291 0 Td
(zinc)Tj
1.8708 0 Td
(rescue)Tj
2.7496 0 Td
(effects)Tj
2.7269 0 Td
(were)Tj
2.126 0 Td
(observed)Tj
3.7927 0 Td
(in)Tj
1.0375 0 Td
(synthetic)Tj
3.8211 0 Td
(limited)Tj
3.0727 0 Td
(zinc)Tj
1.8709 0 Td
(medium)Tj
3.6056 0 Td
(\()Tj
0.83 0.64 0.02 0 k
/F14 1 Tf
(S3)Tj
1.5534 0 Td
(Fig)Tj
0 g
/F8 1 Tf
(\).)Tj
-28.7601 -1.2982 Td
(As)Tj
/F12 1 Tf
1.2699 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.3959 0 Td
(encodes)Tj
3.4355 0 Td
(only)Tj
1.9786 0 Td
(two)Tj
1.7065 0 Td
(predicted)Tj
4.0025 0 Td
(plasma)Tj
3.033 0 Td
(membrane)Tj
4.5638 0 Td
(zinc)Tj
1.8765 0 Td
(importers,)Tj
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(these)Tj
2.2507 0 Td
(data)Tj
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(indicated)Tj
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(that,)Tj
2.0069 0 Td
(in)Tj
1.0318 0 Td
(laboratory)Tj
4.354 0 Td
(medium,)Tj
3.8324 0 Td
(Zrt1)Tj
1.9616 0 Td
(can)Tj
1.6271 0 Td
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(growth)Tj
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(neutral-alkaline)Tj
6.514 0 Td
(pH,)Tj
1.7348 0 Td
(whilst)Tj
-34.3443 -1.2982 Td
(Zrt2)Tj
1.9672 0 Td
(is)Tj
0.8447 0 Td
(essential)Tj
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(for)Tj
1.3889 0 Td
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3.0728 0 Td
(at)Tj
0.9524 0 Td
(acidic)Tj
2.5625 0 Td
(pH.)Tj
1.7291 0 Td
(Based)Tj
2.5455 0 Td
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1.2756 0 Td
(these)Tj
2.2564 0 Td
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3.0727 0 Td
(patterns,)Tj
3.6964 0 Td
(we)Tj
1.3266 0 Td
(hypothesised)Tj
5.4198 0 Td
(that)Tj
/F12 1 Tf
-35.6936 -1.2983 Td
[()47()]TJ
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2.4434 0 Td
(is)Tj
0.8504 0 Td
(specifically)Tj
4.5694 0 Td
(expressed)Tj
4.0932 0 Td
(at)Tj
0.9524 0 Td
(neutral/alkaline)Tj
6.497 0 Td
(pH,)Tj
1.7291 0 Td
(whilst)Tj
/F12 1 Tf
2.6079 0 Td
[()47( )]TJ
/F8 1 Tf
2.4434 0 Td
(expression)Tj
4.4674 0 Td
(is)Tj
0.8447 0 Td
(pH-indepen-)Tj
-31.4983 -1.2983 Td
(dent.)Tj
2.245 0 Td
(We)Tj
1.6044 0 Td
(note)Tj
2.0012 0 Td
(that)Tj
1.7745 0 Td
(this)Tj
1.6781 0 Td
(regulatory)Tj
4.32 0 Td
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(model)Tj
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1.7802 0 Td
(of)Tj
1.0147 0 Td
(the)Tj
-34.9622 -1.3039 Td
(pathogenic)Tj
4.6317 0 Td
(mould)Tj
/F12 1 Tf
2.846 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0998 0 Td
[()-8()12( )18()10()2()22()7()-4()]TJ
/F8 1 Tf
4.1159 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(].)Tj
-11.4972 -1.2982 Td
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1.3379 0 Td
(test)Tj
1.6044 0 Td
(this)Tj
1.6724 0 Td
(hypothesis)Tj
4.4674 0 Td
(we)Tj
1.3266 0 Td
(constructed)Tj
/F12 1 Tf
4.9323 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0658 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.4015 0 Td
(reporter)Tj
3.5036 0 Td
(strains)Tj
2.8573 0 Td
(with)Tj
2.0013 0 Td
(GFP)Tj
2.0182 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(])Tj
1.8539 0 Td
(expression)Tj
-33.2388 -1.2983 Td
(driven)Tj
2.8119 0 Td
(from)Tj
2.2053 0 Td
(either)Tj
2.5342 0 Td
(the)Tj
/F12 1 Tf
1.4683 0 Td
[()47()]TJ
/F8 1 Tf
2.4435 0 Td
(or)Tj
/F12 1 Tf
1.0998 0 Td
[()47( )]TJ
/F8 1 Tf
2.4435 0 Td
(promoters.)Tj
0.83 0.64 0.02 0 k
/F14 1 Tf
4.6261 0 Td
(Fig)Tj
1.542 0 Td
(1B)Tj
0 g
/F8 1 Tf
1.3493 0 Td
(shows)Tj
2.6589 0 Td
(the)Tj
1.4683 0 Td
(expression)Tj
4.4674 0 Td
(profiles)Tj
3.1975 0 Td
(of)Tj
/F12 1 Tf
1.0148 0 Td
[(!)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 558.822 388.4031 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()47()]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 377.0645 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
/F12 1 Tf
1.7291 0 Td
[(!)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 222.8031 375.4204 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()47( )]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 241.6251 377.0645 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(in)Tj
1.0374 0 Td
(low-zinc)Tj
3.6624 0 Td
(medium)Tj
3.6056 0 Td
(at)Tj
0.9524 0 Td
(a)Tj
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(range)Tj
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6.1114 0 Td
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(GFP)Tj
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-30.081 -1.2982 Td
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(by)Tj
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1.1792 0 Td
[(!)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 245.4236 362.4377 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()47()]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 264.3023 364.0818 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
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(activity)Tj
3.118 0 Td
(was)Tj
1.6951 0 Td
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1.6611 0 Td
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(pH)Tj
1.5023 0 Td
(4.6.)Tj
1.6214 0 Td
(However,)Tj
4.0762 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(media)Tj
2.6873 0 Td
(was)Tj
1.7007 0 Td
(neutralised,)Tj
4.8756 0 Td
(fluores-)Tj
-32.8079 -1.2982 Td
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(increased.)Tj
4.2235 0 Td
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1.7008 0 Td
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3.0898 0 Td
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0.9524 0 Td
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1.5024 0 Td
(7.5)Tj
1.4003 0 Td
(than)Tj
2.0296 0 Td
(at)Tj
0.9524 0 Td
(pH)Tj
1.5023 0 Td
(4.6.)Tj
1.6215 0 Td
(At)Tj
1.2018 0 Td
(pH)Tj
1.5081 0 Td
(6.5)Tj
1.3946 0 Td
(and)Tj
1.7291 0 Td
(above,)Tj
/F12 1 Tf
-34.6844 -1.3039 Td
[(!)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 205.5118 336.4157 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()47()]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 222.1228 338.0598 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-GFP)Tj
2.3754 0 Td
(expression)Tj
4.4617 0 Td
(was)Tj
1.7007 0 Td
(significantly)Tj
5.091 0 Td
(higher)Tj
2.8007 0 Td
(than)Tj
2.0295 0 Td
(at)Tj
0.9525 0 Td
(pH)Tj
1.5023 0 Td
(4.6.)Tj
-21.9285 -1.2982 Td
(In)Tj
1.111 0 Td
(contrast,)Tj
/F12 1 Tf
3.685 0 Td
[(!)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 265.4362 323.433 cm
BT
/F12 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()47( )]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 282.1039 325.0771 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-GFP)Tj
2.3697 0 Td
(expression)Tj
4.4674 0 Td
(was)Tj
1.7007 0 Td
(not)Tj
1.5704 0 Td
(as)Tj
1.0148 0 Td
(strongly)Tj
3.4753 0 Td
(affected)Tj
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1.1792 0 Td
(the)Tj
1.4684 0 Td
(pH)Tj
1.508 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(surround-)Tj
-32.7738 -1.2982 Td
(ing)Tj
1.5023 0 Td
(media,)Tj
2.914 0 Td
(with)Tj
1.9956 0 Td
(expression)Tj
4.4673 0 Td
(at)Tj
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(pH)Tj
1.5024 0 Td
(4.6)Tj
1.4003 0 Td
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2.4321 0 Td
(only)Tj
1.9729 0 Td
(2-fold)Tj
2.6192 0 Td
(higher)Tj
2.8006 0 Td
(than)Tj
2.0296 0 Td
(at)Tj
0.9524 0 Td
(pH)Tj
1.5024 0 Td
(6.5.)Tj
1.6214 0 Td
(These)Tj
2.5681 0 Td
(data)Tj
1.9163 0 Td
(are)Tj
1.4456 0 Td
(in)Tj
-36.5949 -1.3039 Td
(agreement)Tj
4.4277 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(previous)Tj
3.6509 0 Td
(study)Tj
2.3924 0 Td
(of)Tj
1.0148 0 Td
(Bensen)Tj
/F12 1 Tf
3.1011 0 Td
[()8()]TJ
0.9127 0 Td
[()11()]TJ
/F8 1 Tf
(.)Tj
1.1679 0 Td
(who)Tj
1.9389 0 Td
(reported)Tj
3.6566 0 Td
(alkaline-)Tj
3.6681 0 Td
(and)Tj
1.7291 0 Td
(acidic-)Tj
2.914 0 Td
(induc-)Tj
-34.0381 -1.2983 Td
(tion)Tj
1.8425 0 Td
(of)Tj
/F12 1 Tf
1.0148 0 Td
[()47()]TJ
/F8 1 Tf
2.4434 0 Td
(and)Tj
/F12 1 Tf
1.7291 0 Td
[()47( )]TJ
/F8 1 Tf
(,)Tj
2.6702 0 Td
(respectively)Tj
4.8869 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
2.0749 0 Td
(However,)Tj
4.0762 0 Td
(from)Tj
2.2053 0 Td
(our)Tj
1.6271 0 Td
(own)Tj
1.9616 0 Td
(observations,)Tj
5.4878 0 Td
(we)Tj
1.3266 0 Td
(conclude)Tj
-33.3464 -1.2983 Td
(that)Tj
1.7744 0 Td
(expression)Tj
4.4674 0 Td
(of)Tj
/F12 1 Tf
1.0148 0 Td
[()47()]TJ
/F8 1 Tf
2.449 0 Td
(is)Tj
0.8448 0 Td
(more)Tj
2.3414 0 Td
(strongly)Tj
3.4752 0 Td
(influenced)Tj
4.4447 0 Td
(by)Tj
1.1792 0 Td
(environmental)Tj
6.1115 0 Td
(pH)Tj
1.5023 0 Td
(than)Tj
/F12 1 Tf
2.0296 0 Td
[()47( )]TJ
/F8 1 Tf
(.)Tj
-30.4381 -1.2982 Td
(These)Tj
2.5682 0 Td
(expression)Tj
4.4672 0 Td
(data)Tj
1.9106 0 Td
(support)Tj
3.3221 0 Td
(our)Tj
1.6271 0 Td
(hypothesis)Tj
4.4617 0 Td
(that)Tj
1.7802 0 Td
(Zrt2)Tj
1.9672 0 Td
(is)Tj
0.8504 0 Td
(essential)Tj
3.583 0 Td
(in)Tj
1.0318 0 Td
(acidic)Tj
2.5625 0 Td
(environments,)Tj
-31.3282 -1.3039 Td
(whilst)Tj
2.6022 0 Td
(either)Tj
2.5341 0 Td
(Zrt1)Tj
1.9672 0 Td
(or)Tj
1.0942 0 Td
(Zrt2)Tj
1.9671 0 Td
(can)Tj
1.6271 0 Td
(support)Tj
3.3165 0 Td
(growth)Tj
3.0784 0 Td
(at)Tj
0.9525 0 Td
(neutral)Tj
3.067 0 Td
(pH.)Tj
1.7292 0 Td
(To)Tj
1.3379 0 Td
(test)Tj
1.6044 0 Td
(this)Tj
1.6724 0 Td
(directly)Tj
3.2315 0 Td
(we)Tj
1.3266 0 Td
(created)Tj
3.1238 0 Td
(a)Tj
/F12 1 Tf
-36.2321 -1.2983 Td
[()-19()]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
(/)Tj
/F12 1 Tf
[()-19( )]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
4.8018 0 Td
(double)Tj
2.9594 0 Td
(mutant)Tj
3.1463 0 Td
(and)Tj
1.7348 0 Td
(performed)Tj
4.4674 0 Td
(more)Tj
2.3414 0 Td
(detailed)Tj
3.3675 0 Td
(growth)Tj
3.0728 0 Td
(kinetics)Tj
3.3051 0 Td
(analysis.)Tj
0.83 0.64 0.02 0 k
/F14 1 Tf
3.5547 0 Td
(Fig)Tj
1.542 0 Td
(1C)Tj
0 g
/F8 1 Tf
-34.2932 -1.2983 Td
(shows)Tj
2.6588 0 Td
(that)Tj
/F12 1 Tf
1.7802 0 Td
[()-19( )]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
2.3471 0 Td
(again)Tj
2.3696 0 Td
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2.16 0 Td
(at)Tj
0.9524 0 Td
(neutral,)Tj
3.2995 0 Td
(but)Tj
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2.5625 0 Td
(pH,)Tj
1.7291 0 Td
(whilst)Tj
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2.6079 0 Td
[()-19()]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
(/)Tj
/F12 1 Tf
[()-19( )]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
4.8075 0 Td
(failed)Tj
2.4038 0 Td
(to)Tj
1.0261 0 Td
(grow)Tj
2.245 0 Td
(at)Tj
-36.0733 -1.3039 Td
(both)Tj
2.0579 0 Td
(pH)Tj
1.508 0 Td
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3.322 0 Td
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1.9842 0 Td
(restored)Tj
3.5036 0 Td
(in)Tj
1.0319 0 Td
(the)Tj
1.4683 0 Td
(revertant)Tj
3.8437 0 Td
(strain)Tj
2.5002 0 Td
(\()Tj
0.83 0.64 0.02 0 k
/F14 1 Tf
(Fig)Tj
1.8879 0 Td
(1C)Tj
0 g
/F8 1 Tf
(\).)Tj
-26.5037 -1.2983 Td
(The)Tj
1.7858 0 Td
(above)Tj
2.5455 0 Td
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3.0726 0 Td
(and)Tj
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4.4673 0 Td
(assays)Tj
2.6249 0 Td
(indicated)Tj
3.9401 0 Td
(that)Tj
1.7745 0 Td
(Zrt2)Tj
1.9672 0 Td
(is)Tj
0.8504 0 Td
(the)Tj
1.4684 0 Td
(dominant)Tj
4.1725 0 Td
(cellular)Tj
3.1351 0 Td
(zinc)Tj
-34.7297 -1.2982 Td
(transporter)Tj
4.7225 0 Td
(in)Tj
/F12 1 Tf
1.0318 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F12 1 Tf
1.0715 0 Td
[()11()14(\r)11()4()7()16()]TJ
/F8 1 Tf
3.3957 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.474 0 Td
(only)Tj
1.9729 0 Td
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3.7984 0 Td
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(acidic)Tj
2.5625 0 Td
(pH.)Tj
1.7292 0 Td
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1.3379 0 Td
(test)Tj
1.5987 0 Td
(this,)Tj
1.9049 0 Td
(wild)Tj
1.9446 0 Td
(type,)Tj
/F12 1 Tf
-35.5348 -1.3039 Td
[()-19( )]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
2.347 0 Td
(and)Tj
/F12 1 Tf
1.7292 0 Td
[()-19( )]TJ
/F13 1 Tf
( )Tj
/F8 1 Tf
(+)Tj
/F12 1 Tf
[()47( )]TJ
/F8 1 Tf
5.1532 0 Td
(were)Tj
2.126 0 Td
(cultured)Tj
3.5659 0 Td
(in)Tj
1.0319 0 Td
(low)Tj
1.661 0 Td
(zinc)Tj
1.8709 0 Td
(medium)Tj
3.6056 0 Td
(\(SD)Tj
1.7689 0 Td
(zinc-dropout,)Tj
5.7089 0 Td
(acidic\),)Tj
3.1238 0 Td
(provided)Tj
-33.6923 -1.2983 Td
(with)Tj
1.9955 0 Td
(25)Tj
/F16 1 Tf
1.1736 0 Td
[()]TJ
/F8 1 Tf
(M)Tj
1.6157 0 Td
(Zn)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 259.37 160.4976 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(++)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 270.2551 156.0755 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
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