Available online at www.sciencedirect.com

ScienceDirect

Adaptive strategies in the double-extremophilic

prokaryotes inhabiting soda lakes

1,2 3

Horia Leonard Banciu and Maria S Muntyan

Haloalkaliphiles are double extremophilic organisms thriving classified within and Bacteria domains of life

both at high salinity and alkaline pH. Although numerous while only few haloalkaliphilic representatives were de-

haloalkaliphilic representatives have been identified among scribed among Eukarya [3]. In-depth investigations of

Archaea and Bacteria over the past 15 years, the adaptations alkaline aquatic systems in western USA [4,5], East

underlying their prosperity at haloalkaline conditions are African Rift Valley [6], and Central Asia [7] showed

scarcely known. A multi-level adaptive strategy was proposed abundant yet considerably distinct microbial communi-

to occur in haloalkaliphilic organisms isolated from saline ties populating saline (NaCl-rich) alkaline and soda (so-

alkaline and soda environments including adjustments in the dium carbonate-rich) lakes, respectively (for reviews see



cell wall structure, plasma membrane lipid composition, [8 ] and [9]; this issue). To overcome the physicochemical

membrane transport systems, bioenergetics, and burden of the high external osmotic pressure (low water

osmoregulation. Isolation of chemolithoautotrophic sulfur- activity, aw) and alkaline pH (low proton concentration

+

oxidizing g-Proteobacteria from soda lakes allowed the [H ]) the haloalkaliphiles must rely on the concurrent

elucidation of the structural and physiological differences mechanisms of cytoplasmic pH homeostasis and osmotic

between haloalkaliphilic (prefer NaCl) and natronophilic (prefer balancing between intra-cellular and extracellular milieus

NaHCO3/Na2CO3, i.e. soda) microbes. as well as on an efficient energetics covering costs not only

Addresses of survival but also remarkable reproductive activity.

1

Institute for Interdisciplinary Research in Bio-Nano-Sciences,

Molecular Biology Center, Babes¸ -Bolyai University, In this review we highlight the latest findings on the

400271 Cluj-Napoca, Romania

2 structural and functional adaptive mechanisms underpin-

Department of Molecular Biology and Biotechnology, Faculty of

ning the growth of haloalkaliphilic prokaryotes thriving in

Biology and Geology, Babes¸ -Bolyai University, 400006 Cluj-Napoca,

Romania the double extreme conditions of high salinity and alka-

3

Lomonosov Moscow State University, Belozersky Institute of Physico- line pH.

Chemical Biology, Moscow 119991, Russia

Corresponding author: Banciu, Horia Leonard ([email protected]) Adaptations in haloalkaliphilic archaea

Presently, alkaliphilic members of Class Halobacteria are

found within isolates from chloride-rich alkaline habitats

Current Opinion in Microbiology 2015, 25:73–79

( pharaonis, Halorubrum tibetense) and soda

This review comes from a themed issue on Extremophiles environments such as Hrr. alkaliphilum, Halobiforma

Edited by Haruyuki Atomi and Elizaveta Bonch-Osmolovskaya nitratireducens, Natronobacterium gregoryi, Natrialba spp.

(Nab. hulunbeirensis, Nab. chahannaoensis, Nab. magadii),

Natronolimnobius spp. (Nln. baerhuensis, Nln. innermongo-

licus), or Natronococcus spp. (Ncc. occultus, Ncc. amylolyticus)

http://dx.doi.org/10.1016/j.mib.2015.05.003 [10]. Besides their optimal pH for growth (8–9.5), another

1369-5274/2015 Elsevier Ltd. All rights reserved. common feature of haloalkaliphilic archaea is the modest

requirement for divalent cations in accordance with the

2+ 2+

low Mg and Ca availability in their original habitat

[10]. In line with this property is the presence of a

tentative calcium-binding outer membrane-like protein

(GeneBank ID 397775179; 176 aa) that seems to be

Introduction unique in the alkaliphilic members of the recently pro-

In 1982, upon isolation of archaeon Natronomonas (former posed Natrialbales order [11].

Halobacterium) pharaonis from a saline alkaline lake in

Wadi An Natrun (Egypt), Soliman and Tru¨ per [1] intro- To date, only a few representatives of haloalkaliphilic

duced the term ‘haloalkaliphilic’ to mark the dual ability archaea were thoroughly tested for the simultaneous

of an organism for growth at high salinity along with adaptations to both high salinity and pH. The haloalk-

alkaline pH. Typical haloalkaliphiles, namely those re- aliphilic Ncc. occultus, isolated from a Kenyan ,

+

quiring 0.5 M of total Na as the lowest limit and produces significant amounts of negatively-charged poly-

pH > 8.5, were postulated to be restricted to saline and (g-glutamine) chains in the cell wall (Fig. 1.1) [12].

alkaline environments such as soda lakes and soda soils Prevalence of acidic residues in the external cell layers

+

[2]. The vast majority of obligate haloalkaliphiles was of alkaliphiles is presumed to attract cations (i.e. Na and

www.sciencedirect.com Current Opinion in Microbiology 2015, 25:73–79 74 Extremophiles

Figure 1

Chemical adjustments in Active cytoplasmic Osmoadaptive strategies

cell wall and membrane pH homeostasis

P CS Na+ Na+ Na+ Archaeal-type 13 cell wall 1 Na+ H+ 12

Plasma 2 membrane 4

+ + + + Na K CI

Haloalkaliphilic archaea H P CS (Natronococcus spp.) (K+) pHopt(37 ºC): 8-9.5 Cytoplasm + [Na }opt: 3-4 M 14 P S

P CS

Gram-positive-type 13 cell wall H+ 12 5 Plasma membrane 4

+ Anaerobic ATP Na K+ CI+

haloalkaliphilic bacteria ADP

Na+ + P CS (K ) (Natranaerobiales) Cytoplasm + Pi H+ pHopt(55 ºC): 9.5 + 14 [Na }opt: 3.3-3.9 M P CS

Flagellum P CS

Outer + 13 Na + membrane Na Na+ Solutes H+

Plasma 3 membrane 9 8 4

+ + Na H P CS + Cytoplasm ADP (K ) ? + + P ATP + Na i 14 Na+ H Aerobic natronophilic H+ H+ P CS Gram-negative bacteria (Thioalkalivibrio spp.) 6 pHopt(37 ºC): 9.8-10.5 7 10 11 + – – [Na }opt: 2-4 M e e + O + O 2 H2O 2 H2O

Halophilic adaptations P Precursors of compatible solutes Alkaliphilic adaptations CS Compatible solutes Mixed (haloalkaliphilic) adaptations Non-extremophilic feature S 2-Sulfotrehalose

Current Opinion in Microbiology

Main adaptive mechanisms in haloalkaliphilic archaea of , Phylum (upper), anaerobic fermentative

NaCl-haloalkaliphilic and thermophilic bacteria of Natranaerobiaceae, Phylum Firmicutes (middle) and aerobic natronophilic bacteria of

Ectothiorhodospiraceae, Phylum Proteobacteria (lower image). Chemical adjustments in cell wall and plasma membrane. Acidic cell wall

Current Opinion in Microbiology 2015, 25:73–79 www.sciencedirect.com

Adaptive mechanisms in haloalkaliphiles Banciu and Muntyan 75

+ À À 2À

H3O ) and repel anions such as Cl , HCO3 , CO3 and (CL), nonpolar squalene, seconded by polar lipids contain-

À

HO . Additionally, Natronococcus spp. have substantial ing unsaturated (C16:1 and C18:1) and cyclopropane fatty

proportions of core lipids containing asymmetric phytanyl acids (cyc-C19) (Fig. 1.3) [22]. Moreover, in Thioalkalivi-

chains (C25, C20) hypothesized to be assembled in a zip- brio halophilus and Thioalkalibacter halophilus, growth at

like structure thus stiffening the plasma membrane and alkaline pH was accompanied by the increase in cyto-



decreasing its ion permeability (Fig. 1.2) [13 ,14,15]. The chrome c oxidase activity and cytochrome c content



genomic analyses of Nmn. pharaonis [16] and Nab. magadii [23 ,24] like in facultatively alkaliphilic strains of Pseudo-

[17] indicated that the osmoadaptive tactics (acidic and monas sp. [25], or extremely haloalkalitolerant Bacillus spp.

moderately hydrophobic proteome, import and synthesis [26]. CL is important in stabilization and function of

of compatible solutes, adaptations to low oxygen by respiratory chain components [27] as well as in salt-stress



formation of gas vesicles, among others) are prevalent response [28] and alkaliphilic adaptation [21 ] whereas

whereas the alkaline adaptations are not so obvious. squalene (C30 isoprenoid) is likely located in the hydro-

Altogether, these findings suggested that the extreme phobic core of the plasma membranes thus possibly com-

haloalkaliphilic archaea are primarily adapted to high salt pacting the lipid bilayer and lowering the membrane

+ +

(>20% w/v NaCl) conditions and grow best at moderate permeability to Na and H [29–31]. Recently, lanosterol

alkaline pH (8–9.5). Remarkably, recent experimental was detected as abundant nonpolar lipid in the membrane

and genomic evidences pointed that the alkaliphilic of Thioalkalivibrio paradoxus (D Sorokin, unpublished da-



such as Natronomonas sp., Natronococcus sp., ta) [32 ] suggesting an important structural function of

Natrialba sp., accumulated 2-sulfotrehalose instead of sterols in the high pH adaptation analogous to that of

trehalose, the latter being preferred as organic osmolyte isoprenoids [33]. Haloalkaliphilic anaerobic bacteria be-

by non-alkaliphilic members of Halobacteriaceae, an alter- longing to Firmicutes (e.g. Tindallia spp., Natroniella spp.,

nate strategy that is yet not well understood (Fig. 1.13–14) Natronincola spp.) contain the unusually large amounts of



[18 ]. unsaturated fatty acids (UFAs), mostly as C16:1v7 and

C18:1v7 [34,35]. Cyclopropane fatty acids (CFAs) are

Haloalkaline adaptations in plasma membrane biochemically derived from UFAs by the assistance of

of soda lake bacteria cyclopropane fatty acid synthase, a conversion that appears

Genus Thioalkalivibrio is a phenotypically and genotypi- to be salt-dependent [22,24]. Overall, fine tuning of mem-

cally diverse group of alkaliphilic obligately chemo- brane fluidity in haloalkaliphiles is probably accomplished

lithoautotrophic sulfur-oxidizing bacteria (SOB) able to by the presence of fatty acids with low melting temperature

+

grow over a broad range of salinity (0.6–4 M of total Na ) (UFAs, CFAs) that compensate for the increased content

at extremely alkaline pH (9.5–10.5). Members of Thioalk- of the nonpolar lipids.

alivibrio sp. are mainly distributed in the soda lakes

worldwide with the exception of Thioalkalivibrio halophi- Molecular structure, gene expression, and functionality

lus and its closely related strains obtained from the saline of membrane transport systems were intensively ex-



alkaline Wadi An Natrun lakes [19,20 ]. plored in halophilic [36] as well as in alkaliphilic bacteria



[21 ], but to a lesser extent in the obligate polyextre-



In a similar manner as in the well-studied alkaliphilic mophiles [32 ,37]. Maintenance of optimal intracellular

 + +

Bacillus strains [for an updated review see [21 ]], Thioalk- [H ] and [Na ], as well as aw in salt-stressed and/or alkali-

alivibrio spp. (e.g., Thioalkalivibrio versutus ALJ15) grown stressed cells is addressed by a multitude of ion channels

both at extremely alkaline pH (10.5) and salinity (2–4 M of (e.g. flagellar stator channels, voltage-gated channels),

+

total Na ) showed high abundance of anionic cardiolipin primary (e.g. V-type or F-type ATPases) and secondary

+ + À À

( Figure 1 Legend Continued ) (in haloalkaliphilic archaea) may attract cations (Na , H ) and repel anions (Cl , HO ) (1); Tightening of plasma

membrane by the presence of asymmetric diether lipids in natronococci (2) and nonpolar lipids in Gram-negative bacteria (3) lowers ion

permeability. Active cytoplasmic pH homeostasis achieved via sodium (potassium) and proton cycling. The monovalent cation/proton antiporters

(CPAs) (4) widely present in Archaea and Bacteria. A large range of multiduplicated CPAs is characteristic of anaerobic haloalkaliphiles (members

of CPA1 and CPA2 families) and aerobic natronophiles (members of CPA1, CPA2 and CPA3 or Mrp-like proteins). In anaerobic thermophilic

+ +

haloalkaliphiles, mainly the Na -motive F-type ATPase expels Na (5); in aerobic natronophiles besides CPAs, the cbb3-type terminal oxidase

+ +

pumps out Na at alkaline pH (6); function of predicted and possibly Na -dependent Rnf complex is obscure (7); smf-driven transporters such as

+ + +

Na /solute symporters (8) and flagellar Na -channels (9) inherent in haloalkaliphiles replenish the intracellular [Na ]; protons are expelled outward

+ +

by H -pumps of respiratory chain (10) and recovered by CPAs (4) and H -motive F-type ATP synthase (11). Osmoadaptive strategies. The ‘salt-in’

strategy (accumulation of inorganic osmolytes such as KCl) is the main osmotic balancing mechanism in Halobacteriaceaea and

+ À + À

Natranaerobiaceae maintained by K and Cl uptake systems (12). While K and Cl import by passive facilitated transport and halorhodopsin,

+ À

respectively, is well documented in haloarchaea, other K /Cl transport systems lack for evidences in the latter group. The ‘salt-out’ strategy

(maintaining of low intracellular salt concentration and accumulation of organic osmolytes such as glycine betaine, ectoine, among others) is the

main osmoadaptive mechanism in aerobic natronophiles and is secondary in haloarchaea and anaerobic Natranaerobiaceae. Active uptake of

compatible solutes and their precursors is documented both in Archaea and Bacteria (13). Additionally, compatible solutes are synthesized de

novo, predominantly as 2-sulfotrehalose in alkaliphilic haloarchaea and glycine betaine, ectoine, among others, in haloalkaliphiles and

natronophiles (14).

www.sciencedirect.com Current Opinion in Microbiology 2015, 25:73–79 76 Extremophiles

+

transporters (cation/proton antiporters — CPAs, Na /sol- high pH environment that gives rise to an inverted pH



ute symporters, among others) [21 ,37]. In alkaliphiles it gradient (i.e. acidic inside) and thus decreases the pmf

was shown that the intracellular pH homeostasis is di- [53]. Consequently, to make up for this energetic unfa-

+

rectly linked to the Na -cycling in a pattern that appears vorable state, most alkaliphiles keep high negative value



well conserved within Bacteria [38 ]. Like in most neu- of membrane electrical potential (Dc) [54]. Indeed,

+

trophilic living cells, the low inner [Na ] in haloalkali- Thioalkalivibrio strains are among them generating Dc

+

philes can be maintained by the secondary Na -expelling of more negative values than À200 mV [55]. Some

+ +

mechanisms, Na /H -antiporters energized by the pro- haloalkalitolerant heterotrophic g-Proteobacteria miti-

+ + +

ton motive force ( pmf) (Fig. 1.4). Mainly the Na /H - gate this problem by employing a sodium (Na )-pumping



antiporters of Nha family and Mrp-type were shown to NADH-CoQ reductase (NQR) [see [56 ] for a recent

+

play roles in Na resistance [39] and survival at high pH review on NQR]. However, the specific genes coding

 + +

[38 ,40,41]. In soda lake aerobic haloalkaliphiles, at the Na -pumping NQR, the only primary Na -pump of

+

alkaline pH, other routes for Na export are likely to the O2-reducing electron-transporting pathway identified

be active. They involve the directly evidenced primarily to date, were not found in genome data for the genus

+

Na -pumping cytochrome oxidase (Fig. 1.6) (also see Thioalkalivibrio which is not surprising, since this locus is



next section) [42,43 ] and perhaps a predicted and exploited for the reversed electron transport in lithoauto-

+

presumably Na -dependent Rnf complex (Fig. 1.7) trophic SOB. Examination of moderately halophilic and

+

[44,45], while the Na -coupled F-ATPases might play extremely alkaliphilic strain of Thioalkalivibrio versutus

+

this role in haloalkaliphilic anaerobes (Fig. 1.5) [37]. evidenced that it possesses a Na -dependent terminal

Except for the haloalkalithermophilic Natranaerobius cytochrome oxidase [57] and recently led us to the dis-

+

thermophilus in which the role of monovalent CPAs in covery of the first oxygen-reducing Na -pump, a cbb3

haloalkaline adaptation was experimentally demonstrat- cytochrome oxidase operating in the membranes of sev-

ed by Mesbah et al. [46], the direct evidences of the eral obligately aerobic alkaliphilic SOB at alkaline pH



activity and function of membrane transport systems in [42,43 ]. According to the genomic information [44,45],

+

haloalkaliphilic bacteria are scarce. Available genome many aerobic natronophiles, besides the Na -motive cy-

+

data of several organisms isolated from soda lakes such tochrome oxidases, also possess H -motive homologues

as Thioalkalivibrio spp. [44,45], Methylomicrobium alcali- which possibly operate at neutral and low alkaline pH or

philum [47], Halanaerobium hydrogeniformans [48,49], under lowered buffer capacity of milieu (Fig. 1.10), while

Spirochaeta africana [50], Chitinivibrio alkaliphilus [51], the FoF1-ATPases presumably serve in them, like in

+

suggest the possible presence in them of several sodium- other aerobic alkaliphiles, solely as the H -motive pumps



motive force (smf) consumers which include the mem- (Fig. 1.11) [38 ,58]. However, physiological function of

+ 2À +

bers of the Na /SO4 -symporter SulP family, Na -de- such ATPases has not been totally elucidated in haloalk-

+

pendent flagellar motor as well as membrane proteins alipiles. Thereafter, the full Na -cycle has not been

with putative roles at alkaline pH and in osmotic stress identified yet in the aerobic natronophiles. Available

response (Fig. 1.8–9; 1.13). experimental and genomic information imply that at high

+

alkaline pH at least a partial Na -cycle functions in these

+

Energetic mechanisms of some explored bacteria which includes a Na -motive cytochrome c oxi-

haloalkaliphiles from soda lakes dase (noted above), as a smf generator exporting sodium

+

A few publications dealt with energetics of soda lake from the cell, and several smf consumers such as Na -

+

bacteria up to now. One of the exciting examples of the motive transporters, symporters, and a Na -type flagellar

typical inhabitants of soda lakes is a group of haloalk- motor noted in the previous section.

aliphilic obligately chemolithoautotrophic SOB which

includes Thioalkalivibrio spp. and Thioalkalimicrobium The choice of organic compatible solute in

spp. Noteworthy, metabolism of these obligately aerobic soda lake bacteria and pivotal difference

SOB representatives is a striking example of chemosyn- between NaCl-haloalkaliphily and

thesis discovered by Winogradski in 1887 [52]. These natronophily

strains derive energy from the aerobic oxidation of re- While the NaCl-dependent haloalkaliphilic archaea and

duced sulfur compounds such as thiosulfate, tetrathio- haloalkalithermophilic bacteria of the order Natranaero-

nate, sulfide, sulfite, and elemental sulfur under high biales adopt the ‘salt-in’ osmoadaptive strategy by accu-

+ +

[Na ] and alkaline pH conditions [for review see mulating K as dominant (but not exclusive) osmolyte



[20 ]]. In particular, in Thioalkalivibrio cells, a periplas- (Fig. 1.12) [10,59], the osmotic response in the vast

mic incomplete sulfur-oxidizing complex (Sox) oxidizes majority of soda lake bacteria is based on the uptake

reduced sulfur compounds, feeding electrons to the re- and de novo synthesis of organic compatible solutes



spiratory chain at the level of cytochrome c [20 ,44,45]. In (Fig. 1.13-14) (e.g. glycine betaine, ectoine, glutamate,



obligately aerobic SOB the electron-transporting pathway sucrose) [32 ]. Although requiring similar energy invest-

of the O2-reducing type is of vital importance. Like all the ments, the choice for accumulation of either ectoine or

alkaliphilic community, they take up a challenge from the glycine betaine as the main osmolyte is tightly linked

Current Opinion in Microbiology 2015, 25:73–79 www.sciencedirect.com

Adaptive mechanisms in haloalkaliphiles Banciu and Muntyan 77

with the physiological limits for salt tolerance. Ectoine is the latter group as compared to the first one. Further

the prevailing organic osmolyte in the low to moderate advancement in studies is required to gain better insight

+

(i.e. up to 2.5 M of total Na ) NaCl-halotolerant, NaCl- into genotypic and phenotypic plasticity (i.e. rapid adap-

halophilic or natronophilic methylobacteria (Methylomi- tation to environmental changes) allowing NaCl-haloalk-

crobium alcaliphilum, M. kenyense, Methylophaga natronica, ali/natronophiles not only to persist but actively

M. alcalica, among others) [60] and chemolithoautotrophic reproduce in their extreme habitats as well as to assess

natronophilic and NaCl-haloalkaliphilic Thioalkalimicro- their potential for biotechnology.

bium spp. and Thioalkalibacter spp. [22,24]. Glycine beta-

ine is the favorite osmolyte for extreme salt-tolerant Acknowledgements



haloalkaliphiles, such as Halorhodospira spp. [61 ], The completion of this review was supported by the Romanian National



Thioalkalivibrio spp. [22,23 ], and Desulfonatronospira Authority for Scientific Research, CNCS-UEFISCDI, to HLB (grant PN-II-

ID-PCE-2011-3-0546) and the Russian Foundation for Basic Research to

spp. [62].

MSM (grant 14-04-01577), while Natronophile database analysis was

supported by the Russian Scientific Foundation to MSM (grant 14-50-00029).

The isolation of two facultatively NaCl-haloalkaliphilic,

extremely salt-tolerant SOB Thioalkalivibrio halophilus

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