2.1. Polysaccharides

Polysaccharides are mainly divided into two categories, namely heteropolymers and homopolymers. These polysaccharides can be uncharged or charged, repeating or non-repeating, and un-branched or branched. A plethora of bacteria can produce polysaccharides and reserve them within their cells, such as glycogen, or they may also secrete polysaccharides, which are attached to the cell surfaces or free exopolysaccharides that help in the matrix formation in biofilms (cellulose and alginate mainly) ^[7]. On being motile, pathogenic organisms produce various virulence factors and other toxic substances such as exotoxins. On the other hand, while in sessile state, pathogens produce different exopolysaccharides such as cellulose, alginate, and hyaluronate, acting as components of biofilm matrix. This shifting to sessile biofilm state defines the onset of chronic infectious diseases, since the encapsulated or embedded cells are shielded from host immune responses and anti-microbial drugs ^[11]. For example, alginate present inside the matrix of biofilm in Pseudomonas aeruginosa contributes to enhancing the surviving chances of the bacterial cells by shielding them from phagocytosis ^[1]. Alginates react with divalent cations forming dense hydrogels with increased water-retention capacity ^[20]. Again, cellulose production accounts for identical advantages to enterococcal pathogens ^[21]. Escherichia coli is known to produce phosphoethanolamine cellulose that can form a mortar-like structure for stabilization of proteinaceous curli fibers. These fibers strongly interconnect the biofilm forming cells, providing resistivity against conditions of high stress ^[22]. Other pathogens like Bacillus cereus G9241 and Streptococcus pyogenes consist of a capsule made of hyaluronate, which is a linear heteropolysaccharide with negative charge and a structural homolog of hyaluronate that is found in the connective tissues of humans. Thus, these pathogens can easily escape from being exposed to phagocytosis and opsonization. Serogroup B Neisseria meningitidis leads to invasive diseases of meningitis because of the presence of the capsular polysaccharide consisting of sialic acid homopolymers (N-acetylneuraminic acid) having α-2, 8 sialic acid bonds. This polymeric structure of the moieties of polysialic acid resembles the structure of the antigens present in human tissues, and this molecular analogy accounts for reduced immunogenic properties of the capsular polysaccharides, thereby rendering the pathogen non-immunogenic to the host ^[23]. Streptococcus pneumoniae is one of the leading pathogens in causing severe lung diseases and consists of over 100 serotypes producing diverse capsular polysaccharides for evasion of adaptive host immune response ^[24]. Capsular and secreted polysaccharides are widely used as antigens for producing conjugate vaccines. Designing of serotype-independent vaccines is increasing because of the varying serotypes of N. meningitidis and S. pneumoniae, which decreases the effectiveness of these vaccines ^[1]. Glycogen is a water-soluble polymer consisting of α-1, 6 and α-1, 4 glycosidic linkages, and it is the most well-known form of carbon and energy reserve for survival during starvation. In case of intracellular infections, glycogen helps the pathogens like Salmonella enterica subsp. Mycobacterium tuberculosis and Chlamydia trachomatis to survive ^[25] (Figure 1).

Figure 1. Mechanism of bacterial polymer synthesis pathway. FAB: fatty acid de novo biosynthesis; FAD: fatty acid β-oxidation; KDPG: 2-keto-3-deoxy-6-phosphogluconate pathway; NDP: nucleoside 5ʹ-diphosphate; P: phosphate; PGI: phosphoglucoisomerase; PGM: phosphoglucomutase; Pha: polyhydroxyalkanoate synthesis enzyme; TCA cycle: tricarboxylic acid cycle.

Glycogen is secreted from the capsular polysaccharides that are associated with the surface of the cell and result in the development of the matrix of the biofilm ^[7]. Alginates that are produced by P. aeruginosa are responsible for the protection of the cells from phagocytosis ^[1]. Phosphoethanolamine cellulose produced by E. coli helps in the stabilization of fibers, which in turn form a complex biofilm by interlinkage of these fibres and develop resistance against high shear conditions. E. coli produces phosphoethanolamine cellulose, which forms mortar-like structures to stabilize proteinaceous curli fibers. These fibers mediate strong connections between cells in complex biofilms and provide resistance in high-shear conditions. Hyaluronate produced by Streptococcus pyrogens and Bacillus cereus helps in mimicking hyaluronate being present within the connective tissues, thus protecting them from phagocytosis ^[26]. It has also been observed that capsular polysaccharide comprising of sialic acid produced by Neisseria meningitides resembles the polysialic moieties of human antigen, thereby making it invisible within the host exerting its pathogenicity ^[23].

Apart from acting as virulence factors, bacterial polysaccharides exhibit distinctive materialistic properties. Synthesis of polysaccharides chemically is tedious, expensive, and restricted to low molecular weight molecules and could be done only for a few types of polysaccharides. Thus, microbial cell factories are essential for manufacturing these polymers. As hydrophilic groups (carboxyl and hydroxyl groups) are present on the polysaccharides, these polysaccharides actually have high water-retention capacity allowing crosslinking (polymer–polymer, drug–polymer, host tissue–polymer, and cellular interactions) and intermolecular interactions. Polysaccharides are able to form porous hydrogels to be used in drug delivery and controlled delivery of anti-cancer drugs ^[27], enzyme immobilization ^[28], and therapeutic entrapment of cells, thereby protecting transplanted cells from the host immunity ^[29] and tissue engineering ^[30]. Hydrogels that are made from bacterial cellulose can serve as efficient matrices, fiber composites, or hydrogel nanofibrillar scaffold network, having biomedical applications such as wound dressing that can deliver human dermal fibroblasts and epidermal keratinocytes ^[24]. Cellulose from Komagataeibacter xylinus finds application in large scale production of rayon-based fibers to be used as wearable textiles. Hyaluronate produced by non-pyogenic Streptococcus zooepidemicus also has wide biomedical applications ^[31]. Commercialized formulations of hyaluronate forms a gel-like fluid that can be used in injections to treat arthritis pain in knee joints.

Some enzymes naturally alter the materialistic properties of polysaccharides to modify their biological functions. For example, the existence of acetyl groups on chains of polysaccharides remarkably modify structural conformities, thereby affecting chain–chain interactions, water-retention capacity, solubility, molecular weight, and viscoelasticity ^[32]. Using genetically engineered polysaccharide-modifying enzymes in microbial cell factories or using these enzymes to modify polysaccharides in vitro allows the generation of tailor-made polysaccharides. The fabrication of these materials after modification changes on being blended with other non-polymeric or polymeric components (esterification of stearic acid, crosslinking of citric acid, and plasticizers). Blending accounts for modification of properties like degree of gelation, viscoelasticity, material strength, and porosity. These materials are being used as feedstock components and as bioinks in 3D bioprinting with varied engineering and biomedical applications like drug testing and drug delivery and tissue engineering. 3D cell-loaded scaffolds made from hyaluronate or alginate can be extensively used as artificial extracellular matrix (ECM), providing for a temporary environment for supporting adhesion, invasion, proliferation, and differentiation of different types of cells such as fibroblasts, mesenchymal stem cells, embryonic stem cells, chondrocytes, and osteoblasts ^[33]. Thus, bacteria can be considered as an important natural source for the secretion of a wide variety of polysaccharides having medicinal uses and potential industrial applications (Table 1).

2.2. Polyamides

Bacteria are capable of producing polyaminoacids or polyamides like secreted poly-L-lysine and poly-D-glutamic acid or the intracellularly produced cyanophycin (copolymer of L-arginine and L-asapartic acid), and they can serve as biofilm matrix components or capsular polymer and also storage materials ^[35]. Just like the polysaccharides of biofilm matrix, polyamide biofilm or capsule is less immunogenic, thereby protecting pathogens like Bacillus anthracis from being attacked by the host immune system ^[33]. Polyamide-based materials are also produced by various non-pathogenic bacteria such as Bacillus megaterium, Bacillus licheniformis, and many of the cyanobacteria ^[36]. Polyamides have high charges and may be polycationic or polyanionic. They are considered as non-toxic, biodegradable, and renewable. Metabolic engineering helps in the production of biotechnologically enhanced polyamides. Polyamides potentially substitute chemically produced polymers in industries. For example, poly-D-glutamic acid can be utilized as a flocculant for replacing synthetic flocculants (polyacrylamide or polyaluminium chloride) for treating wastewater ^[34]. Poly-L-lysine possesses antibacterial properties, since it can disrupt the integrity of membrane, thereby damaging the cross links, and is used in antimicrobial coatings ^[34].

2.3. Polyesters

Polyhydroxyalkanoates (PHA) are bacterially produced bioplastics. They have a linear symmetry and are arranged in hydrophobic spheric inclusion, functioning as a carbon and energy reserving material ^[10]. Even though many gram-negative and gram-positive bacteria can secrete PHAs, the functions of PHAs and the potential genes involved in PHA-mediated pathogenesis and persistence are still unknown. PHA

 mutants of 

 reveal decreased attachment to surfaces of glass and diminished stress tolerance in presence of biofilms, therefore revealing a significant contribution of PHA in persistence in infections ^[37]. In one of the plant pathogens 

 (causes major rice production losses), the regulatory protein called PhaR represses the synthesis of PHA and also suppresses EPS production, thus affecting virulence and phenotypic changes modifying lifestyle of the bacteria ^[38]. PHAs are reported to be electron sinks, which in anaerobic conditions (terminal electron or oxygen absence) enhance survival ^[38]. Synthesis and mobilization of PHA are controlled under responses such as environmental stimuli and environmental and nutritional stresses, rendering an advantageous survival.

PHAs are known to be a distinctive bioplastic that can be chemically modified or bioengineered to be used as high-value medical biomaterials such as scaffolds in tissue engineering, sutures, particulate vaccines, and drug carriers or to be used as low-value bioplastic ^[34]. Synthesis of tailor-made PHAs through physical blending, bioengineering, or chemical modification produced enhanced materialistic properties that met the requirements of medical and industrial usage. Microbial cell factories can be biologically engineered to produce PHA inclusions that can be heavily coated with proteins of functional interest. These functionalized beads of PHA were stable even after being separated from the cell mass of bacteria, indicating high-value performance as immunodiagnostics, vaccines, enzyme carriers, bio separation resins, and tools required in the production of recombinant proteins. Additionally, the functional performance of these protein-coated, non-porous beads of PHA can be tuned further by regulated encapsulation inside porous microspheres of alginate allowing flow-through usage [39,40]^[39][40].

2.4. Polyphosphates

Polyphosphate (polyP) is a polymer consisting of condensed phosphates (several inorganic phosphates), which have a high negative charge along with high-energy anhydride bonds. PolyP serves as an energy storing polymer. PolyP biosynthesis results from an evolutionary activity of bacteria, and this helps in providing chemical energy for the various biosynthetic pathways inside bacterial cells and can act as buffers against bases. Additionally, polyPs can act as a metal chelating agent contributing to the formation of channel complexes in order to uptake DNA. PolyPs aid in cell signalling regulation, thus affecting the lifestyle of bacteria, their growth, persistence, viability, virulence, and stress tolerance ^[41].

Since polyPs can eminently act as an energy-storing material, they have been widely used in industries to provide energy in carrying out enzyme-catalyzed reactions. They are used as biologically active biomaterials in the production of regenerative medicines for repairing cartilages and in the regeneration of bones or can be also used as vehicles for drug-delivery. As polyPs can react with cationic polymers (like hyaluronate and alginate), inorganic cations (like Mg²⁺, Ca²⁺, Zn²⁺, Na⁺, Fe²⁺, and K⁺) or other organic alkaline components (like peptides, polyamines, and amino acids), they can be converted into hydrogels or nanoparticles to be used in biomineralization of bones ^[42] or for various biomedical uses. Essentially, physical properties like functionality and stability and mechanical durability of polyP-associated complex nanoparticles or hydrogels may change depending upon the class of blended polymeric substances or interacting counterions. This modification furnishes considerable space designing for the generation of a wide variety of materialistic properties for bioinks and smart biomaterials in regenerative medicines. Living organisms, particularly bacteria, are considered as the only source of polyp, since there are no known abiotic polyP minerals found on Earth. Bacteria of the genera Corynebacterium and Mycobacterium can produce granules of polyP with increased yield and therefore can be used as potential producers for polyP manufacture ^[43].

2.5. Other Bacterial Polymers

Bacteria can even produce various types of biopolymers that can act as proteinaceous components and extracellular DNA. These types of biopolymers are not only responsible for pathogenesis in bacteria, but can be also used for biomaterial production. Extracellular DNA forms when a cell is lysed, releasing the intracellular DNA. In the case of biofilms, a cellular subpopulation lyses to produce extracellular DNA, like for example in stalks of mushroomlike microcolonies formed by P. aeruginosa ^[44]. Because of the high negative charge, extracellular DNA has multiple roles in the adherence and stability of the matrix of biofilm by interaction with cationic polysaccharides (like Pel) and other cations and can also act as a source of nutrients at times of starvation conferring resistivity to antibiotics.

Secreted polypeptides are composed of alternating hydrophobic and hydrophilic residues of amino acids and proteins like pilin, fibrillin, and flagellin. These polypeptides can serve as molecular elementary units to form extracellular self-built structures like pili, fimbiriae, flagella, and functional amyloids such as curli fibers. These self-assembled structures are capable of forming nanotubes or nanofibers, mediating cell adhesion on abiotic and biotic surfaces, developing matrix of biofilm, or providing motility during pathogenesis. Various features like increased ratio of surface area to volume, the explicit arrangement of building blocks of proteins, and polymorphic transformations of these structures are a result of their responses against chemical and physical stimulations, making them a potential component in industrial and biomedical applications. These properties make them important biomaterials and bio templates for the designing of novel nanodevices, nanostructures, and multiple layered lattices to be used in nanomedicines (drug delivery) and bioengineering ^[45]. The genetic programmability and the simplicity of engineering polypeptides, proteins, and extracellular DNA make them attractive for manufacturing programmable biomaterial-based platforms, which can be hardly manufactured with other types of biopolymers like polyesters and polysaccharides. Moreover, the uncomplicated genetic programmability helped in the development of bioengineered living materials in which the live cells are bioengineered for autonomous self-assembly of all the materials, having tunable and novel properties for different purposes like microbial electrosynthesis, electronic devices for monitoring, biosensors, and bioremediation ^[46].

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