Advances in Antarctic Research for Antimicrobial Discovery: A Comprehensive Narrative Review of Bacteria from Antarctic Environments as Potential Sources of Novel Antibiotic Compounds Against Human Pathogens and Microorganisms of Industrial Importance

The recent emergence of antibiotic-resistant bacteria has become a critical public health problem. It is also a concern for industries, since multidrug-resistant microorganisms affect the production of many agricultural and food products of economic importance. Therefore, discovering new antibiotics is crucial for controlling pathogens in both clinical and industrial spheres. Most antibiotics have resulted from bioprospecting in natural environments. Today, however, the chances of making novel discoveries of bioactive molecules from various well-known sources have dramatically diminished. Consequently, unexplored and unique environments have become more likely avenues for discovering novel antimicrobial metabolites from bacteria. Due to their extreme polar environment, Antarctic bacteria in particular have been reported as a potential source for new antimicrobial compounds. We conducted a narrative review of the literature about findings relating to the production of antimicrobial compounds by Antarctic bacteria, showing how bacterial adaptation to extreme Antarctic conditions confers the ability to produce these compounds. We highlighted the diversity of antibiotic-producing Antarctic microorganisms, including the phyla Proteobacteria, Actinobacteria, Cyanobacteria, Firmicutes, and Bacteroidetes, which has led to the identification of new antibiotic molecules and supports the belief that research on Antarctic bacterial strains has important potential for biotechnology applications, while providing a better understanding of polar ecosystems.

the specific isolation of Actinobacteria. Even though Antarctic bacteria grow under low temperatures and survive freezing, optimal growth temperatures for isolates usually range from 4 • C to 20 • C, since Antarctic bacteria includes psychrotrophic and psychrophilic organisms [17]. Aerophyllic isolation conditions are usually preferred; therefore, aerobic organisms are typically isolated. However, microaerophilic bacterial strains, containing the anaerobic global regulator gene (anr), have been also reported [46], as well as obligate anaerobes [47,48].
Antarctic marine soils are free of snow and ice during the summer months and receive nutrients from the ocean and animal life-penguin guano, for example, enriches the soils with nitrogen and phosphorus, thus creating an environment capable of supporting abundant microbial growth [24]. O'Brien et al. [17] also show that all ornithogenic soil samples yielded high bacterial counts (6-9 log CFU·g −1 ) in comparison to other samples. Very high counts (10 log CFU·g −1 ) have been reported in ornithogenic soil through direct microscopic counting [49].
The presence of frozen water in Antarctic soils often leads to an increase in soil solute concentration, resulting in the creation of a hypersaline microenvironment [50]. Consequently, bacterial isolation in terms of colony-forming units from maritime Antarctica soils is higher in NaCl-containing media [17], showing the predominance of halotolerant bacteria in this habitat. In addition, high altitude soils in the Trans-Antarctic Mountains provide the least hospitable environment for microbial growth, since temperatures rise above freezing for only brief periods each year. Predictably, soils at over 1000 m above sea level contained low levels of microorganisms [17].
Although research on Antarctic microbial ecology began in the early 1900s [24], the region is still considered to be a potentially exploitable ecosystem for the discovery of new microorganisms with potential benefits for humans, due to its vast, unexplored diversity and peculiar environmental conditions. Bacteria with antimicrobial activity have been isolated from various Antarctic habitats, predominantly soils and seawater (Table 1). Higher antibiotic activity is typically produced by attached bacteria rather than their free-living counterparts in the pelagic zone [51,52]. This phenomenon might be due to the production of antimicrobial metabolites, which in a free-living stage could produce needless energy waste. Antagonistic interactions could play a key role in colonizing an ecological niche with high densities of bacteria [51,53], preventing other bacteria from colonizing particles. Although occurring less frequently, antimicrobial activity from free-living marine bacteria has also been reported and is reviewed in the following sections.

Bacterial Adaptation to Antarctic Extreme Conditions Might Confer the Ability to Produce Diverse and Novel Antimicrobial Compounds
Due to their extreme environment, Antarctic bacteria have been reported as a potential source for antimicrobial compounds [61]. Microorganisms need to develop different strategies to survive polar conditions [76,77], such as lack of substrate, high UV-radiation, sustained low temperatures, and short-term intense heat during the Antarctic summer [23]. These complex conditions represent diverse challenges for bacterial life, including reduced enzyme activity, decreased membrane fluidity, altered transport of nutrients and waste products, decreased rates of transcription, translation, and cell division, protein cold-denaturation, inappropriate protein folding, and intracellular ice formation [78].
Therefore, genetic adaptation of Antarctic microorganisms to polar stress factors would be expected to generate novel metabolic pathways through evolutionary selection [76]. Thus, one can suggest the synthesis of new metabolites from Antarctic bacteria with unique structures and specific biological activity, produced as a competitive advantage for niche colonization by establishing antagonistic relationships [23].
Such antagonistic interactions among Antarctic bacteria have been demonstrated [79], and numerous Antarctic bacterial isolates exhibited antagonistic properties against marine bacteria from the same environment [80]. Differences were observed in the inhibition patterns of single isolates, suggesting that their activity was more likely strain-specific rather than dependent on phylogenetic affiliation [79]. Similarly, five Actinobacteria strains were isolated from surfaces of Antarctic macroalgae and showed activity against other macroalgae-resident bacteria, both Gram-negative and Gram-positive strains [80]. This data suggest the potential exploitation of Antarctic bacteria as a novel source of antimicrobial compounds and confirms antagonistic interactions within bacterial strains in Antarctic marine ecosystems.
Reports on Pseudoalteromonas spp. also support the case for discovering Antarctic bacteria suitable for the production of antimicrobial metabolites. This genus has become a model for studying bacterial adaptation to cold, since it is frequently isolated from marine polar regions [81][82][83]. Genomic analysis of the Antarctic strain Pseudoalteromonas haloplanktis TAC125 has demonstrated important features relating to its adaptability [84]. Among them a specific codon usage bias, which is involved in the resistance to protein aging features including asparagine cyclization and deamination [85]; the resistance to reactive oxygen species (ROS), which represent a significant stressor under cold conditions [86,87]; and the elevated number of rRNA and tRNA genes, which could explain its translational efficiency even in cold conditions [67]. Additionally, cryotolerance and osmotic stress resistance have been conferred by the enhanced uptake of compounds including: Spermine, Glutathione, Ornithine, and others, related to Glutathione metabolism; increased metabolic potential in terms of Arginine and Proline metabolism, β-Alanine metabolism, fatty acid uptake, and biosynthesis; and protein S-thiolation [88]. Similarly, carotenoid pigmentation confers protection to Antarctic bacteria against freeze-thaw cycles and solar radiation [89].
Another approach using the existing genomes of Pseudoalteromonas isolates has shown important evolutionary implications regarding the diverse genetic information of cold-adapted bacteria, including the relatively high number of genes obtained through horizontal gene transfer-12,981 genes (14% of the genome) were associated with mobile genetic elements-and an extensive evolutionary genome reduction of this genus [84]. These modifications probably acted as the main factors leading to the genomic diversity between Pseudoalteromonas strains, and might correspond to other isolated Antarctic bacteria.
On the other hand, it is reasonable to believe that strains isolated from the Antarctic might possess genes involved in the adaptation to cold temperatures, such as Anti-Freeze Proteins (AFPs), a class of proteins able to inhibit ice nucleation or decrease the water freezing point temperature [90,91]. Remarkably, recent studies revealed no clear distinction between Antarctic and non-Antarctic Pseudoalteromonas strains, with all of them showing four to five AFPs [84]. This could be a genus-specific feature.
Regarding antimicrobial compounds, Bosi et al. [84] demonstrated that Antarctic Pseudoalteromonas genomes harbor at least one cluster involved in bioactive molecule synthesis, with the number of clusters per genome ranging from 1 to 19. As expected, high variability of biosynthetic operons was confirmed in terms of number and composition across the different genomes [84]. Furthermore, experimental evidence has shown the production of broad-spectrum antimicrobial compounds by Antarctic Actinobacteria preferentially at lower temperatures [60]. This behavior and genetic evidence supports the assumptions that Antarctic bacteria use antimicrobial compounds as an advantage to compete for nutrients and space in the cold environment.

Proteobacteria Phylum Members
A screening for bioactive secondary metabolites showed that 25% (14 out of 57) of Proteobacterium species isolated from Antarctic soils generate an extracellular crude extract that is highly bioactive against Candida albicans and Staphylococcus aureus. The most bioactive genus was Bradyrhizobium, which contributed 64% of the total bioactive isolates in the study (9 out of 14) [11]. However, genera Methylobacterium, Paracoccus, and Sphingomonas were bioactive as well [11]. Other screenings also report the antimicrobial activity of Halomonas sp. strains against a broad range of human pathogens, including the Gram negative Salmonella enterica, Escherichia coli, Enterobacter aerogenes, Citrobacter freundii, Serratia marcescens, Shigella flexnerii, Shigella sonnei, Staphylococcus aureus, and Staphylococcus epidermidis, and the Gram positive Enterococcus faecalis and Listeria monocytogenes [63].
Strains belonging to Pseudoalteromonas genus expressed antagonistic activity against E. coli and Proteus mirabilis [14] and several members of Bcc [65], inhibiting their growth primarily due to the synthesis of numerous volatile compounds (VOCs). Remarkably, this study reported a constitutive synthesis of the volatile antimicrobial compounds (not induced by the presence of target strains), suggesting that production of such molecules is a common feature for the Antarctic strains [65]. Additionally, P. haloplanktis TAC125 produces a saccharidic compound that lacks antibacterial activity against free-living bacteria, but exhibits specific activity against biofilms formation of S. epidermidis strains isolated from infected catheter and septic arthritis [66]. Other studies have identified antibiotic compounds from different Pseudoalteromonas sp. strains isolated from marine environments, including extracellular active agents [92], molecules against methicillin-resistant pathogens [93], and genetic clusters related to the synthesis and regulation of antimicrobial compounds [94].
Since different Pseudoalteromonas sp. strains have shown important bioactive characteristics, this taxon is used as a model for molecular studies on the potential of Antarctic bacteria. In particular, Antarctic isolates have a great number of biosynthetic operons producing antimicrobial compounds, and pigmented Pseudoalteromonas sp. strains are characterized by the presence of a higher number of operons [84]. This result agrees with bioactivity assays where pigmented Pseudoalteromonas sp. exhibited the largest inhibition [95]. Other authors have highlighted the antimicrobial potential of pigmented bacteria from Antarctic marine environments [80]. Consequently, it has been proposed that those strains are able to produce a wider array of bioactive molecules, since they have a larger number of antimicrobial-producing operons [84].
Additionally, novel Proteobacteria species with antimicrobial activity have been found in the Antarctic. Lysobacter oligotrophicus was first described as a new member of the genus Lysobacter, which are strongly proteolytic and characteristically lyse a variety of microorganisms, as well as nematodes. L. oligotrophicus produced esterase, amylase, and protease, and showed a capacity to lyse Gram negative bacteria (E. coli, Lysobacter enzymogenes, and Rhodoligotrophos appendicifer) and Saccharomyces cerevisiae. Indeed, autolysis of this strain was observed in the stationary phase [64].

Actinobacteria Phylum Members
It is well known that bacteria from the phylum Actinobacteria represent a prominent source of biologically active natural compounds, since they produce versatile secondary metabolites [8]. Moreover, Actinobacteria are one of the major phyla of the domain bacteria, comprising 17 orders [96,97]. Remarkably, Actinobacteria comprise the genus Mycobacterium (a deadly bacterial pathogen), but also Streptomyces genus, which are most important for antibiotic production and are responsible for two-thirds of all known antibiotics [98].
Katz and Baltz [8] reported that bacteria belonging to this phylum have the capacity to produce around 30 to 50 secondary metabolites, making them one of the major sources of natural compounds. However, in recent years, the discovery of new antibiotic molecules from Actinobacteria has been infrequent, in part due to the recurrent genetic exchange between species from similar ecosystems [10]. As a result, the latest studies are focused on a search for Actinobacteria from unusual and isolated environments in order to discover novel antimicrobial metabolites [99,100].
Antarctic investigations have shown promising results with antimicrobial active compounds from Actinobacteria. A Streptomyces sp. strain capable of inhibiting the growth of seven Gram negative food borne pathogens (from genera Vibrio, Enterobacter, Klebsiella and Salmonella) and eight Gram positive food borne pathogens (from genera Listeria, Bacillus, Enterococcus and Staphylococcus) was isolated from Antarctic soil [60]. Likewise, strains of Arthrobacter sp. were found to produce active compounds against a broad range of human pathogens, including Gram positive, Gram negative, yeast (B. subtilis, B. cereus, M. luteus, P. aeruginosa, A. johnsonii, Candida sp., Cryptococcus sp., Listeria spp. and B. thermosphacta) [17,56] and several Bcc strains [54]. Moreover, 22 marine Antarctic strains belonging predominantly to Arthrobacter sp., Janibacter thuringensis, Nesterenkonia sp., and Rhodococcus fascians expressed antagonistic activity against E. coli, M. luteus, B. subtilis, and P. mirabilis [14]. Similar results have been reported for other Rhodococcus sp. strains isolated from Antarctic ornithogenic soils [56].   [57] reported extracellular bioactive metabolites from 38% (15 out of 39) of Actinobacterial isolates, inhibiting the growth of C. albicans, methicillin-resistant S. aureus, and P. aeruginosa. Brevibacterium genus showed the highest activity, with five bioactive isolates [57]. Although the 15 isolates with antibiotic activity were obtained from soil samples at the same location, the isolates turned out to be taxonomically diverse, since the strains belong to 11 different genera (Nocardioides, Gordonia, Micromonospora, Demetria, Rhodococcus, Janibacter, Dermacoccus, Kocuria, Lapillicoccus, and Brevibacterium). These findings confirm the abundant bacterial diversity in Antarctic environments. Comparably, Gordonia terrae, Leifsonia soli, and Terrabacter lapilli isolated from Antarctic volcanic soils showed inhibitory activity against S. enterica serotype Paratyphi and S. enterica serotype Enteritidis [58]. Other marine Actinobacteria have been reported to have antimicrobial activity against numerous human pathogens. In fact, novel species have been found to exhibit at least one of the biosynthetic genes coding for polyketide synthases and non-ribosomal peptide synthetases [18] related to the production of these secondary metabolites [101].
Furthermore, Nocardioides sp. belonging to Actinobacteria phylum isolated from Antarctic soil showed extracellular antimicrobial activity against Gram positive and Gram negative bacteria, especially S. aureus and B. subtilis. Preliminary analysis showed that the compounds with antimicrobial activity produced by this strain are mainly glycolipids and/or lipopeptides. Remarkably, the type of compound and specific activity against S. aureus depended on the used carbon source [59]. This finding is important because the antimicrobial substances might be produced mainly by the secondary metabolite pathway, depending on nutritional conditions and probably based on different chemical signals from the environment, as reported for other Antarctic isolates [55,68,102]. Hence, nutritional factors, such as carbon and nitrogen sources, metal ions, and inorganic phosphate in the media, may affect the production of secondary metabolites during cultivation of the microorganisms. This could be a critical aspect to consider for screening and discovering antimicrobial compounds produced by bacteria.

Other Phylum Members
A dominance of Cyanobacterial diversity in Antarctic and other polar environments has been reported by Vincent [103] and Zakhia et al. [104], indicating that the search for antimicrobial compounds from Antarctic Cyanobacteria seems to have a promising future. Interestingly, novel Antarctic Cyanobacteria was described as having antibacterial/antifungal potential. Some unknown and uncultured Cyanobacterial strains with antibiotic activity were found through 16S ribosomal RNA gene (16S rRNA) and ITS sequence analysis [104]. From 48 total isolates, 35% of the strains (identified as Pseudophormidium sp., Phormidium priestleyi, Leptolyngbya antarctica, Nostoc sp. and Phormidium murrayi) showed activity against S. aureus, or the fungi Aspergillus fumigatus and Cryptococcus neoformans in a strain-specific manner, using ethyl acetate and methanol crude extracts [71,105]. Activity against M. tuberculosis, S. aureus, S. typhi, P. aeruginosa, Enterobacter aerogenes and multidrug-resistant strains of E. coli, was also reported for extracts of Antarctic Nostoc sp. strains [72].
On the other hand, bioactivity of Firmicutes phylum has been occasionally reported from Antarctic isolates; however, O'Brien et al. [17] reported for the first time the isolation of Planococcus sp. strains from Antarctic soil with the production of bioactive compounds against Gram positive human pathogens (Listeria spp. and B. thermosphacta). In addition, a proteinaceous compound from Enterococcus sp. isolated from penguin rookeries and belonging to Firmicutes phylum exhibited a strong effect against multidrug-resistant strains of C. albicans [75]. Bacillus sp. and Sporosarcina sp. strains isolated from Antarctic soils demonstrated activity against yeast (Candida sp. and Cryptococcus sp.), Gram positive (B. subtilis, B. cereus, S. lutea, and methicillin resistant S. aureus) and Gram negative bacteria (P. aeruginosa, E. coli, and A. johnsonii) [56,74].
Similarly, Mojib et al. [62] first described an Antarctic Flavobacterium sp. belonging to Bacteroidetes phylum, with activity against M. smegmatis and M. tuberculosis. In addition, an Antarctic Pedobacter sp. strain, a member of this phylum, was reported for the first time as producing inhibitors against human pathogens (E. coli, S. enterica, K. pneumoniae, E. cloacae, and B. cereus) [69]. Additionally, in a high throughput screening for antimicrobial activity, 675 strains were isolated from 17 samples of benthic mats collected from 10 lakes located in three distinct Antarctic regions and 18% were active against at least one of the panel pathogens (S. aureus, E. faecium, and E. coli). Some of the active bacteria were members of phyla Actinobacteria and Proteobacteria; however, most of the isolates belong to Bacteroidetes, while others could not be assigned to any classification based on 16S rRNA analysis [55].

Antarctic Bacterial Strains Exhibit Activity against Microorganisms of Industrial Importance
Unlike the inhibitors produced by mesophylls, the antimicrobials produced in cold environments, such as the Antarctic, need to function at low temperatures for the organisms to gain a competitive advantage during their growth cycle. Such cold-active antimicrobial compounds may be exploitable in industrial applications, including chilled-food preservation [17].
Furthermore, Antarctic bacterial isolates have shown potential against biofilm formation, which is of great importance for different industrial applications. For example, Leyton et al. [70] reported that 26.9% of Antarctic bacterial isolates (from a total of 67) strongly inhibited the biofilm of Flavobacterium psychrophilum, with the greatest effect shown by proteins (48-56 kDa) secreted by Pseudomonas fragi strains. F. psychrophilum affects farmed salmon and trout worldwide and its ability to form biofilms, in addition to the emergence of resistant strains, have increased the resistance to antibiotics [70].
Furthermore, Nocardioides sp. belonging to Actinobacteria phylum isolated from Antarctic soil showed extracellular antimicrobial activity against Xanthomonas oryzae, which is one of the most harmful diseases of rice, causing bacterial blight [59]. Similar results against these phytopathogens have been reported for other Actinobacteria isolates (Arthrobacter sp.), Proteobacteria (Pseudomonas sp. and Burkholderia sp.), and Firmicutes strains (Sporosarcina sp.) [56]. Additionally, at least three Halomonas sp. strains isolated from Antarctic sea water showed activity against multiple phytophatogen species, including Xanthomonas axonopodis, Xanthomonas albilineans, Erwinia stewartii, and Erwinia amylovorans [63]. This indicates that Antarctic strains represent a valuable and almost unexplored source of bioactive molecules for biocontrol of plant diseases, representing a worldwide need.

Recent Advances Identified New Antibiotic Molecules from Antarctic Bacteria
Although just a limited number of antibiotic molecules from Antarctica bacteria have been purified and described, most of them correspond to new molecules (Figure 1). In a study reporting an analysis of a total set of six antimicrobial-producing bacteria by high-resolution mass spectrometry, the resulting exact mass of the purified extracts did not match any known compound in the natural products library for any of the analyzed strains [55]. In addition, some of the purified fractions could not be associated with complete antimicrobial activity, suggesting that one Antarctic isolate may represent a source of numerous new antimicrobial compounds, which might act synergistically against competing microorganisms. Furthermore, the production of methylamine by P. haloplanktis TAC125, with anti-Bcc activity, was demonstrated by VOCs capture, accumulation, and storage, followed by solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS). Despite this finding, methylamine only partially contributes to the effect against Bcc; thus, the efficiency of marine Antarctic bacteria to inhibit almost all Bcc strains may be related to the synergistic effect of multiple unknown VOCs [68].
Additionally, an antibacterial molecule from the Antarctic Cyanobacterium Nostoc sp. was elucidated based on UV, IR, NMR, electron impact mass spectra (EIMS), and electronspray ionization mass spectra (ESIMS) data [72]. The structure of the active principle was proposed as 4-[(5-carboxy-2-hydroxy)-benzyl]-1,10-dihydroxy-3,4,7,11,11 pentamethyloctahydrocyclopenta<a>naphthalene, which is an intracellular biomolecule with broad-range antibacterial activity. This molecule is similar to anthraquinone and indane derivatives of a diterpenoid and different from the various biomolecules reported from Nostoc species other than of Antarctic origin. The rate of production of the active principle corresponds to 1.70 mg·g −1 biomass dry weight [72].
Antibiotics 2018, 7, 16 of 22 samples, with antimicrobial and antitumor activity [23]. Additionally, Asencio et al. [61] reported the presence of violacein in an antibiotic ethanolic extract from Janthinobacterium sp., which also contains other undetermined compounds that can act as synergistic agents with violacein. The pigmented compound of the other Antarctic Janthinobacterium sp. strain was determined by NMR as (3-[5-(3-hydroxyl-1H-indol-3yl)-2-R1-1H-pyrrol-3-ylidene]-2-R1-1H-indol), with some differences for other violacein pigments previously reported [62]. In the same study, the structure of additional pigment obtained from Antarctic Flavobacterium sp. was elucidated and described as the first reported flexirubin with antimicobacterial activity [62]. Three other soluble compounds from Pseudomonas sp. strain with activity against Bcc strains and S. aureus were elucidated by high-resolution electrospray ionization mass spectrometry (HRESIMS), Three other soluble compounds from Pseudomonas sp. strain with activity against Bcc strains and S. aureus were elucidated by high-resolution electrospray ionization mass spectrometry (HRESIMS), NMR, and LC-MS as rhamnolipids as follow: (1) C 28 H 52 O 9 , containing two fully saturated lipid chains; (2) C 28 H 50 O 9 , with one ester, one carboxylic acid group, two olefinic carbons, an anomeric carbon, A and B chains having 10 and 12 carbons, respectively, and a single unsaturation at B5; and (3) C 30 H 54 O 9 , with A and B chains and a single unsaturation at B7 [54]. The first compound was already known [109], but the last two compounds were reported as new rhamnolipids with antimicrobial activity. Rhamnolipids are well-known secondary metabolites synthesized by members of different Gram negative species. They perform several functions in bacteria, including surface motility and biofilm development [110]. Recently, they have emerged as potential antimicrobials against a broad range of pathogens, due to their intercalation into biological membranes leading to cell death by a permeabilizing effect [111].

Concluding Remarks
Bacteria isolated from the Antarctic environment are an unexploited source of novel antimicrobial compounds, which may be advantageous in food, therapeutic, health, and industrial applications in the future. Data about Antarctic microorganisms producing antimicrobial compounds are scant in comparison to other extensively studied environments. Although we exposed numerous bacterial strains from different phyla with various antibiotic activity, it is difficult to evaluate and compare the data generated from the different authors, due to the diversity of variable parameters in the screening process, such as isolation circumstances, target selection, and assay conditions. Consequently, it is important to increase investigations focused on antimicrobial activity from Antarctic bacteria in order to amplify comparable available data.
Despite most reports showing Antarctic bacterial strains as a source of antibiotic compounds, the samples/isolates lacked large-scale, high-throughput bioprospection, showing results only for a limited panel of target pathogens and usually just one condition-crude extract. Therefore, developing and applying robust screening models and high-throughput methods is of great importance for studying antimicrobial activity from single or multiple Antarctic bacterial strains in order to increase the chances for the discovery and identification of novel antibiotic molecules. To achieve this goal, it is imperative that the experimental design include all possible variables, such as recovering intra-and extracellular extracts produced in different growth conditions, using possible inducers of antimicrobial activity, and testing against a larger number of targets. To our knowledge, just one study exists where a robust screening model was applied, focusing on the search of antimicrobial activity from Antarctic bacteria, which analyzed 6348 extract samples that were tested in two or three media with different incubation periods and extraction methods [55].
The search for Antarctic microorganisms that could have industrial applications started only in the late 20th century and relatively few scientific groups are pursuing this research. Since then, only a few antibiotic molecules have been purified and elucidated; however, most of them correspond to new molecules. As a result, further work is needed for the identification and purification of new strains, and characterization of the chemical structures of new antibiotics with pharmacological or industrial applications. Geographical locations already covered by research in the Antarctic are limited (Figure 2), particularly on the west side of the continent, and a clear-cut correlation is lacking between the antimicrobial activity pattern and taxonomical distribution of bacterial strains in the Antarctic regions [55]. Thus, there is a great opportunity to continue the discovery and characterization of new antimicrobials from unexplored Antarctic regions. Furthermore, this review does not consider reports of bacteria with antimicrobial activity isolated from Antarctic organisms. Nevertheless, there are reports of their ability to inhibit pathogens, for example for bacteria isolated from sponges [112][113][114] and macroalgae [115]. Therefore, there could be other unusual habitats within the Antarctic that are suitable for the discovery of antimicrobial compounds. Reported diversity of Antarctic bacteria producing antimicrobial compounds and the geographical locations where diverse sample types were collected for isolation. Different phyla diversity has been reported for west and east Antarctic (a); each phylum has been reported with different frequency for the west side (b) compared to the east counterpart (e). Geographical locations where bacteria with antimicrobial activity have been isolated at each Antarctic side are shown, indicating that the west side has been less explored (d). Blue marks represent regions where punctual sampling was executed; green marks joined by a line illustrate two studies [14,17] where the complete area was sampled; the amplified squares show regions with multiple sampling sites. Active strains have been isolated utilizing different sample sources for west (c) and east (f) continent sides, including soil and seawater for both areas, and freshwater and microbial mats on the west side. Reported diversity of Antarctic bacteria producing antimicrobial compounds and the geographical locations where diverse sample types were collected for isolation. Different phyla diversity has been reported for west and east Antarctic (a); each phylum has been reported with different frequency for the west side (b) compared to the east counterpart (e). Geographical locations where bacteria with antimicrobial activity have been isolated at each Antarctic side are shown, indicating that the west side has been less explored (d). Blue marks represent regions where punctual sampling was executed; green marks joined by a line illustrate two studies [14,17] where the complete area was sampled; the amplified squares show regions with multiple sampling sites. Active strains have been isolated utilizing different sample sources for west (c) and east (f) continent sides, including soil and seawater for both areas, and freshwater and microbial mats on the west side.
Finally, we have demonstrated the importance of better research on the inhibitory power of Antarctic strains from a clinical and industrial point of view, but additional Antarctic bioprospecting is necessary in order to understand the role of novel antibacterial molecules in structuring microbial, polar communities from an ecological point of view. There is little information available on the interactions between organisms in polar ecosystems, and very little is known in particular about the microbial diversity and functional capacity of the Antarctic permafrost compared to the Arctic, where the majority of comprehensive metagenomic studies have been done [116]. The application of -omics methods on Antarctic systems will provide an important understanding of microbial diversity, functional capacity of the ecosystem, novel antibiotic molecules, and their role in microbial community modulation. Moreover, as recently highlighted by Mocali et al. [88], multi-omics analyses are needed to generate information that could contribute to filling the gap between genotypic and phenotypic features relating to bacterial cold-adaptation mechanisms. In conclusion, research on Antarctic bacterial strains represents an important potential for biotechnology, while providing a better understanding of polar ecosystems.