THE BACTERIA: THEIR ORIGIN, STRUCTURE,FUNCTION AND ANTIBIOSIS

The Bacteria: Their Origin,Structure, Function and Antibiosis

by

Arthur L. KochIndiana University,Bloomington, IN, USA

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Table of Contents

Preface .................................................................................. viiLegend to the Frontispiece .......................................................... ix

Part 1 Origin of Bacteria

1. The Origin of Life Based on Physical Principles ................................ 3

2. Preamble to Life.................................................................... 9

3. The First Cell ....................................................................... 15

4. Development of Cell Physiology and Diversity.................................. 21

Part 2 Wall Structure

5. Covalent Bonds and Tensile Strength of Materials .............................. 39

6. Structure of the Fabric that Covers a Bacterium................................. 49

7. The Covalently Linked Sacculus: the Nona-Muropeptide Model .............. 61

8. The Structure of the Tessera; the Unit Structure of Murein Wall............... 71

9. Extrusion and Incorporation into Wall ............................................ 77

10. The Role of Poles in the Growth Strategy of Bacteria .......................... 81

Part 3 Bacterial Morphologies

11. Sidewalls of Gram-Negative Rod-Shaped Bacteria.............................. 91

vi Table of Contents

12. Growth Strategies for Gram-Positive Cells....................................... 99

13. Wall Growth Strategies for Gram-Negative Cells ............................... 109

14. Commas, Vibrios, Spirilla, and Helicobacters; Tapered andBranched Bacteria.................................................................. 119

15. Spirochetes and Spiroplasma and the Special Strategies for CWD(Cell Wall Deficient) Cells ........................................................ 137

16. Coccal Versus Rod-Shaped Cells, and the First Bacterium ..................... 147

17. Diseases: Old and New ............................................................ 161

Part 4 Antibiosis

18. Lysozymes as Alternatives to β-lactams Antibiotics Acting on theBacterial Wall ...................................................................... 181

19. Development of Wall Antibiotics and Bacterial Counter-Measures ........... 185

20. Antibiotics and Resistance, with an Emphasis onAminoglycosides................................................................... 201

21. Future Chemotherapy Aimed at the Bacterial Murein .......................... 209

References.............................................................................. 217

Preface

This book may seem like three or four books even though the main fo-cus is on a specialized topic—the bacterial cell wall. Its job is to formulate theinnovations that caused life to initiate on earth, those that caused cell physiologyto develop without diversity developing, those that allowed the murein walls ofthe cells to arise, those that led to the separation of the domain of Bacteria fromother organisms, those that allowed the Archaea and the Eukarya to developindependently, and those that then led to the development of a very diverse bio-sphere. It must have taken a long time after the origin of the first cell; evolutionhad to proceed to produce very effective organisms. At some point a collectionof very similar organisms arose that were first called collectively the Last Uni-versal Ancestor (LUA), and stable divergence developed from there. The firstbacterium had a protective cell wall and its descendants developed in many di-verse evolutionary directions, gave rise to many species of bacteria with variouslife strategies, and expanded to fill the many niches in the collection.

As the kingdoms or domains of Archaea and Eukarya evolved, manyof these organisms (and even some bacteria) acted against bacteria. The devel-opment of antibiotics acting on the wall of bacteria and lytic enzymes, calledlysozymes, produced by protozoa, plants and animals, led to destruction of manybacteria. These antagonistic challenges to bacteria resulted from its own cell wallstructure. This structure was both bacteria’s most prominent advantage and itsgreatest liability. It led to growth success of bacteria and to development of awidespread domain—and to their destruction by other organisms. Man subse-quently extended and elaborated these destructive tricks against bacteria, whichled to the antibiotic era of medicine. Sometimes however, medical progress hasturned out to be retrograde to long term medical advances. The attempt here ispresent the physics, chemistry and the evolution of life forms that created targetsfor antibiotics and the bacterial response to antibiotics. Logically all aspects mustbe considered together in order that new treatments for infection will not onlywork but will be effective for a long time.

Most of today’s bacteria maintain a peptidoglycan or murein wall (calleda sacculus or exoskeleton) that surrounds them completely. This strong wallprotects them against osmotic differences between the inside and the outside

viii Preface

that otherwise might lead to the influx of water and the resultant rupture of thecell, but it also has many roles in the biology of bacteria. This book focusesfirst on the chemistry and mechanics of the cell’s wall formation and functionand how evolutionary forces probably led to its development. The makeup andstructure of the wall permit bacteria to occupy diverse habitats and niches. Itallows bacteria to do the same things that larger, multicellular organisms do,but in different ways. The book questions and tries to answer: (1) How does thebacterial envelope enlarge safely with the maintenance of cell shape? (2) Howdoes the wall function as a critical cell organelle for other vital bacterial needs? (3)How does division of the sacculus and the bacterial cell occur? (4) How do otherliving organisms (the Archaea, Eukarya, and particularly, Homo sapiens) combatbacteria? (5) How have bacteria evolved in the recent past to overcome humanproduction and distribution of wall-directed antibiotics? The ideas presented arelogical conclusions from what we do know, but only tentative answers can begiven because ideas about early evolution and more recent evolution have beendeduced largely from properties of modern organisms and the current knowledgeof molecular genomics.

Arguments throughout the book are mustered to illustrate that prokary-otic life is more directly and simply dependent on physical and chemical princi-ples than are the life forms of multicellular organisms. Of course, either directlyor indirectly, the exploitation of physical laws and chemical reactions is depen-dent on Darwin’s three principles. In modern translation these are (1) replicationof informational biomolecules must be accurate most of the time; (2) only occa-sionally do mutations take place, and (3) the translation into functional workingforms takes place from the information propagated in molecular form. The roleof antibiosis in evolution and man’s attempt to use it is for his own advantageinclude the successes and the failures. In the future, the concepts presented inthis book, I am certain, will be critical for medical advances in treatment ofinfectious diseases.

Legend to the Frontispiece:

The Structural Elements of the Bacterial Wall:Five Disaccharide Penta-muropeptides Forminga Glycan Chain and Two about to Form aNona-muropeptide

Seven penta-muropeptides of Escherichia coli or Bacillus subtilis areshown in this frontispiece. The top portion shows a glycan chain formed from fiveNAG (N-Acetyl-Glucosamine) and five alternating NAM (N-Acetyl-Muramicacid) residues. The NAM residues are each linked with penta-muropeptides. Theconformation of the glycan chain is a spiral with the top and bottom muropeptidesin the same plane. The middle one is also in the same plane but points in theopposite direction. Two of these structures in mirror images are bound to eachother by transpeptidation with the loss of the terminal d-Alanine (d-Ala) groupsthat are shown enclosed in blue ovals. This forms a tessera as shown moreexplicitly in Figs. 8.1 and 8.2. The bacterial sacculus is formed of many suchtesserae and completely encloses the cell.

In the formation of a crossbridge the d-Alanine would be removed inthe transpeptidation process and resulting disaccharide tetra-muropeptide cou-pled by endopeptide bonds (tail-to-tail bonds) with another disaccharide penta-muropeptide to form nine-membered nona-muropeptide. Other muropeptidesare shown in the top part of the figure, two pointing above and two pointingbelow the plane of the cell; they either remain as such or are degraded. Theremaining muropeptide is in the plane but points in the opposite direction.

In the bottom part of the figure, the terminal d-Ala groups are againshown in blue and the zwitter ionic groups of the diaminopimelic acid groupsare indicated within yellow ellipses. They are placed correctly, but the bondingis not shown because they are part of the diaminopimelic acid group. This aminoacid is abbreviated A2pm (and also DAP in the literature) Diaminopimelic acidminus the dipeptide d-Ala-d-Ala and also minus the zwitter group is designatedfor clarity by ZZ. Two penta-muropeptides are shown positioned for the removalof the terminal d-Ala and formation of the tail-to-tail bond with a aminogroup of the zwitter ion. The two ways that this can be done are indicated. Oneprecludes the other, but the remaining unbound d-Ala-d-Ala and the zwitter of

x Legend to the Frontispiece

the diaminopimelic acid have ionic attraction to each other and this stericallyprecludes entry of additional muropeptides or the endo-transpeptidase enzyme asthe nona-muropeptide molecule is originally formed. However, when the formednona-muropeptide is stressed enough by growth to break the ionic attachmentof these two groups, then entry becomes allowed and further growth is possible.